Mir-10 microRNA precursor family
Encyclopedia
The miR-10 microRNA precursor is a short non-coding RNA
gene involved in gene regulation. It is part of an RNA gene family which contains miR-10, miR-51, miR-57, miR-99 and miR-100. miR-10, miR-99 and miR-100 have now been predicted or experimentally confirmed in a wide range of species. (MIPF0000033, MIPF0000025) mir-51 and mir-57 have currently only been identified in the nematode Caenorhabditis elegans
(MIPF0000268, MIPF0000271). microRNAs are transcribed as ~70 nucleotide
precursors and subsequently processed by the Dicer
enzyme
to give a ~22 nucleotide product. In this case the mature sequence comes from the 5'
arm of the precursor. The mature products are thought to have regulatory roles through complementarity
to mRNA.
n animals. It is one of the most widely distrubuted microRNAs in animals, it has been identified in numerous species including human, dog
, cat
, horse
, cow, guinea pig
, mouse
, rat
, common marmoset
(Callithrix jacchus), common chimpanzee
(Pan troglodytes), rhesus monkey (Macaca mulatta), Sumatran orangutan
(Pongo abelii), northern greater galago
(Otolemur garnettii), grey short-tailed opossum
(Monodelphis domestica), northern treeshrew
(Tupaia belangeri), European rabbit
(Oryctolagus cuniculus), African bush elephant
(Loxodonta africana), nine-banded armadillo
(Dasypus novemcinctus), European hedgehog
(Erinaceus europaeus), lesser hedgehog tenrec
(Echinops telfairi), zebra finch
(Taeniopygia guttata), chicken
, platypus
(Ornithorhynchus anatinus), Western clawed frog
(Xenopus tropicalis), Carolina anole
(Anolis carolinensis), zebrafish (Danio rerio), Japanese pufferfish
(Fugu rubripes), green spotted pufferfish
(Tetraodon nigroviridis), Japanese killifish
(Oryzias latipes), three-spined stickleback (Gasterosteus aculeatus), Florida lancelet
(Branchiostoma floridae), California purple sea urchin
(Strongylocentrotus purpuratus), 12 different species of fruit fly (Drosophila
), Western honey bee (Apis mellifera), mosquito (Anopheles gambiae
), red flour beetle
(Tribolium castaneum), the nematode Caenorhabditis elegans
, owl limpet
(Lottia gigantea), starlet sea anemone
(Nematostella vectensis) and the blood fluke Schistosoma japonicum
. In some of these species the presence of miR-10 has been shown experimentally, in others the genes encoding miR-10 have been predicted computationally.
are found within the Hox gene clusters. In mammals there are four Hox gene clusters, these contain five genes encoding miRNAs (mir-10a, mir-10b, mir-196a-1, mir-196a-2 and mir-196b). The mir-10a gene is located upstream of Hoxb4
and the mir-10b gene is located upstream of Hoxd4
. Zebrafish have seven Hox gene clusters, genes encoding miR-10 (mir-10a, mir-10b-1, mir-10b-2 and mir-10c) are found in the Hox Ba, Bb, Ca and Da clusters. A fourth miR-10 gene (mir-10d) is found elsewhere in the genome, at a location homologous to the pufferfish HoxDd cluster.
of the precursor while in the beetle Tribolium castaneum most production comes from the 5' arm
. These changes of arm preference during evolution are termed arm switching events, and they are relatively frequent during the evolution of microRNAs.
s of mice. Lower levels of miR-10a are seen in small intestine
, lung
and spleen
, and lower levels of miR-10b are seen in skeletal muscle
. Expression of miR-10b has also been detected in the ovaries. Adult zebrafish express miR-10a in heart
, testis and ovary, and miR-10b in muscle and liver
.
In developing embryos, miR-10 is detected at specific stages. Zebrafish embryos show miR-10a expression from 48 to 120 hours post-fertilisation
, and miR-10b expression from 12 to 120 hours post-fertilisation.
In Drosophila expression of miR-10-3p is highest in 12 to 24 hour old embryos and in 1st and 3rd instar
larvae
. Levels of miR-10-5p are highest in 12 to 24 hour old embryos and much lower in larvae.
In stage 5 Drosophila embryos (130–180 minutes post-fertilisation), miR-10 is distributed throughout 50-80% of the length of the egg. Later in development miRNA-10 becomes localised into bands, and levels decrease by stage 7 (195–200 minutes post-fertilisation). miR10 reappears by stage 11 (320–440 minutes post-fertilisation), where it is found in the ventral nerve cord
, posterior midgut
and hindgut
. At stage 14 (620–680 hours post-fertilisation), miRNA-10 is localised to the posterior midgut and the anal pad. In Drosophila larvae, miR-10-3p is found in the imaginal disc
s (groups of cells
which are destined to become adult structures upon metamorphosis
). Expression of miR-10ba in mouse embryos shows a similar pattern to that of the Hoxb4 gene. Highest levels are found in the posterior trunk of the embryo, surrounding the hindlimb buds
. Similarly, expression is restricted to the posterior trunk of chicken embryos. In Zebrafish embryos expression of miR-10 is also restricted to the posterior trunk, later in development it is further restricted to the spinal cord
.
s which are important in embryonic development. In zebrafish embryos, miR-10 binds to sites in the three prime untranslated region
(3'UTR) of the HoxB1a and HoxB3a genes, which are important in anterior-posterior patterning during embryonic development. Binding of miR-10 leads to the repression
of these genes. It also acts synergistically
with HoxB4 to repress these genes. The mir-10 gene is located near to the HoxB1a and HoxB3a genes within the zebrafish genome, Hox-1 and Hox-3 paralogues located on different Hox clusters are not targets of miR-10. Human HOXD10
gene has also been shown experimentally to be repressed by miR-10a and miR-10b.
It has also been experimentally verified that miR-10a downregulates the human HOXA1 and HOXA3
genes. Control of the Hox genes by miR-10 suggests that this microRNA may play an important role in development.
In addition to the Hox genes, miR-10a represses the transcription factor USF2
and the Ran
and Pbp1 genes.
miR-10a binds to the five prime untranslated region
(5'UTR) of mRNAs encoding ribosomal proteins, and increases their translation
. It binds immediately downstream of the 5' oligopyrimidine
tract (5'TOP) motif, a region important in the regulation of ribosomal protein synthesis
.
s. Upregulation of miR-10 has been found in a number of cancers. Increased levels of miR-10a have been found in glioblastoma
, anaplastic astrocytoma
s, primary hepatocellular carcinoma
s and colon cancer
. Increased levels of miR-10b have been found in glioblastoma, anaplastic astrocytomas, pancreatic cancer
, and metastatic
breast cancer
. Although high expression of miR-10b is found in metastatic breast cancers, it does not appear to be present at high levels in early breast cancers.
Downregulation of miR-10a has been found in chronic myeloid leukemia
. USF2, a target gene of miR-10a, has been found to be overexpressed in these leukemias. Downregulation of miR-10a has also been found in acute myeloid leukemia
, the most common acute leukemia
affecting adults. Conversely, miR-10a and miR-10b have found to be upregulated in acute myeloid leukemia with NPM1
mutation
s; these account for approximately a third of adult acute myeloid leukemia cases and contain mutations in the NPM1 gene which result in the relocation of NPM1 from the nucleus
to the cytoplasm
. Upregulation of miR-10b has also been found in B-cell chronic lymphocytic leukemia, the most common type of leukemia.
Genomic copy number abnormalities involving microRNA genes (both increases and decreases in copy number) have been found in cancers. A gain in copy number of the mir-10a gene has been found in melanoma
and breast cancer.
Upstream of the mir-10b gene is a promoter region containing a binding site for the Twist transcription factor
(Twist). Binding of Twist to this promoter region induces
miR-10b expression, leading to a reduced translation of the tumour suppressor
HOXD10. This results in upregulation of RhoA
/RhoC
, Rho kinase
activation and tumour
cell invasion.
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...
gene involved in gene regulation. It is part of an RNA gene family which contains miR-10, miR-51, miR-57, miR-99 and miR-100. miR-10, miR-99 and miR-100 have now been predicted or experimentally confirmed in a wide range of species. (MIPF0000033, MIPF0000025) mir-51 and mir-57 have currently only been identified in the nematode Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
(MIPF0000268, MIPF0000271). microRNAs are transcribed as ~70 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
precursors and subsequently processed by the Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
to give a ~22 nucleotide product. In this case the mature sequence comes from the 5'
Directionality (molecular biology)
Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. The chemical convention of naming carbon atoms in the nucleotide sugar-ring numerically gives rise to a 5′-end and a 3′-end...
arm of the precursor. The mature products are thought to have regulatory roles through complementarity
Complementarity (molecular biology)
In molecular biology, complementarity is a property of double-stranded nucleic acids such as DNA, as well as DNA:RNA duplexes. Each strand is complementary to the other in that the base pairs between them are non-covalently connected via two or three hydrogen bonds...
to mRNA.
Species distribution
The presence of miR-10 has been detected in a diverse range of bilateriaBilateria
The bilateria are all animals having a bilateral symmetry, i.e. they have a front and a back end, as well as an upside and downside. Radially symmetrical animals like jellyfish have a topside and downside, but no front and back...
n animals. It is one of the most widely distrubuted microRNAs in animals, it has been identified in numerous species including human, dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
, cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
, horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
, cow, guinea pig
Guinea pig
The guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
, mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
, rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
, common marmoset
Common Marmoset
The common marmoset is a New World monkey. It originally lived on the Northeastern coast of Brazil, in the states of Piaui, Paraiba, Ceará, Rio Grande do Norte, Pernambuco, Alagoas and Bahia...
(Callithrix jacchus), common chimpanzee
Common Chimpanzee
The common chimpanzee , also known as the robust chimpanzee, is a great ape. Colloquially, the common chimpanzee is often called the chimpanzee , though technically this term refers to both species in the genus Pan: the common chimpanzee and the closely related bonobo, formerly called the pygmy...
(Pan troglodytes), rhesus monkey (Macaca mulatta), Sumatran orangutan
Sumatran Orangutan
The Sumatran orangutan is one of the two species of orangutans. Found only on the island of Sumatra, in Indonesia, it is rarer and smaller than the Bornean orangutan. The Sumatran orangutan grows to about tall and in males...
(Pongo abelii), northern greater galago
Northern Greater Galago
The northern greater galago , also known as Garnett's greater galago, is a prosimian primate endemic to Africa.A low-coverage genomic sequence of the northern greater galago, was completed in 2006...
(Otolemur garnettii), grey short-tailed opossum
Gray Short-tailed Opossum
The gray short-tailed opossum is a small member of the Didelphidae family of opossums. It was the first marsupial to have its genome sequenced. It is naturally found in arboreal habitats in Bolivia, Brazil and Paraguay. The opossum is used as a research model in science, and is also frequently...
(Monodelphis domestica), northern treeshrew
Northern Treeshrew
The Northern Treeshrew is a species of treeshrew found in Southeast Asia.It was chosen as one of the 16 mammals to have their genomes sequenced by the Broad Institute, and a low coverage assembly of genome was released by the Broad Institute in June 2006. The genome will be useful in comparisons...
(Tupaia belangeri), European rabbit
European Rabbit
The European Rabbit or Common Rabbit is a species of rabbit native to south west Europe and north west Africa . It has been widely introduced elsewhere often with devastating effects on local biodiversity...
(Oryctolagus cuniculus), African bush elephant
African Bush Elephant
The African Bush Elephant or African Savanna Elephant is the larger of the two species of African elephant. Both it and the African Forest Elephant have usually been classified as a single species, known simply as the African Elephant...
(Loxodonta africana), nine-banded armadillo
Nine-banded Armadillo
The nine-banded armadillo , or the nine-banded, long-nosed armadillo, is a species of armadillo found in North, Central, and South America, making it the most widespread of the armadillos...
(Dasypus novemcinctus), European hedgehog
European Hedgehog
The European Hedgehog , Common hedgehog or just Hedgehog in the anglophone parts of Europe, is a hedgehog species found in northern and western Europe. It is about 20 to 30 cm in length. Adult mass typically ranges from 600 to up to 1,200 g ; occasionally, it may reach as much as...
(Erinaceus europaeus), lesser hedgehog tenrec
Lesser Hedgehog Tenrec
The Lesser Hedgehog Tenrec is a species of mammal in the Tenrecidae family.It is the only species in the genus Echinops and is named in honour of Charles Telfair.-Distribution and habitat:It is endemic to Madagascar...
(Echinops telfairi), zebra finch
Zebra Finch
The Zebra Finch, Taeniopygia guttata, is the most common and familiar estrildid finch of Central Australia and ranges over most of the continent, avoiding only the cool moist south and the tropical far north. It also can be found natively in Indonesia and East Timor...
(Taeniopygia guttata), chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
, platypus
Platypus
The platypus is a semi-aquatic mammal endemic to eastern Australia, including Tasmania. Together with the four species of echidna, it is one of the five extant species of monotremes, the only mammals that lay eggs instead of giving birth to live young...
(Ornithorhynchus anatinus), Western clawed frog
Western clawed frog
The Western clawed frog is a species of frog in the Pipidae family, also known as Tropical clawed frog or Silurana tropicalis. It is the only species in the Xenopus genus to have a diploid genome...
(Xenopus tropicalis), Carolina anole
Carolina anole
The Carolina anole is an arboreal lizard found primarily in the southeastern United States and some Caribbean islands. Other common names include the green anole, American anole and red-throated anole...
(Anolis carolinensis), zebrafish (Danio rerio), Japanese pufferfish
Fugu
is the Japanese word for pufferfish and the dish prepared from it, normally species of genus Takifugu, Lagocephalus, or Sphoeroides, or porcupinefish of the genus Diodon. Fugu can be lethally poisonous due to its tetrodotoxin; therefore, it must be carefully prepared to remove toxic parts and to...
(Fugu rubripes), green spotted pufferfish
Tetraodon nigroviridis
Tetraodon nigroviridis is one of the pufferfish known as the green spotted puffer. It is found across South and Southeast Asia in coastal freshwater and brackish water habitats. Tetraodon nigroviridis reaches a maximum length of about 15 cm...
(Tetraodon nigroviridis), Japanese killifish
Oryzias latipes
Oryzias latipes, also known as Medaka and Japanese killifish, is a member of genus Oryzias , the only genus in the subfamily Oryziinae. This rather small...
(Oryzias latipes), three-spined stickleback (Gasterosteus aculeatus), Florida lancelet
Lancelet
The lancelets , also known as amphioxus, are the modern representatives of the subphylum Cephalochordata, formerly thought to be the sister group of the craniates. They are usually found buried in sand in shallow parts of temperate or tropical seas. In Asia, they are harvested commercially as food...
(Branchiostoma floridae), California purple sea urchin
Strongylocentrotus purpuratus
The purple sea urchin, Strongylocentrotus purpuratus, lives along the eastern edge of the Pacific Ocean extending from Ensenada, Mexico to British Columbia, Canada. This sea urchin species is deep purple in color and lives in lower intertidal and nearshore subtidal communities...
(Strongylocentrotus purpuratus), 12 different species of fruit fly (Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
), Western honey bee (Apis mellifera), mosquito (Anopheles gambiae
Anopheles gambiae
Anopheles gambiae is a complex of at least seven morphologically distinguishable species of mosquitoes in the genus Anopheles. This complex was recognised in the 1960s and includes the most important vectors of malaria in sub-Saharan Africa and the most efficient malaria vectors known.This species...
), red flour beetle
Red flour beetle
The red flour beetle is a tenebrionid beetle. It is a worldwide stored product pest.Red flour beetles attack stored grain products causing loss and damage...
(Tribolium castaneum), the nematode Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
, owl limpet
Lottia gigantea
Lottia gigantea, common name the owl limpet, giant owl limpet or solitary giant owl limpet, is a species of sea snail, a true limpet, a marine gastropod mollusc in the family Lottiidae...
(Lottia gigantea), starlet sea anemone
Starlet sea anemone
The starlet sea anemone is a species of sea anemone native to the east coast of the United States, with introduced populations along the coast of southeast England and west coast of the United States....
(Nematostella vectensis) and the blood fluke Schistosoma japonicum
Schistosoma japonicum
Schistosoma japonicum is an important parasite and one of the major infectious agents of schistosomiasis.This parasite has a very wide host range, infecting at least 31 species of wild mammals, including 9 carnivores, 16 rodents, one primate , two insectivores and three artiodactyls and therefore...
. In some of these species the presence of miR-10 has been shown experimentally, in others the genes encoding miR-10 have been predicted computationally.
Genomic location
The mir-10 genesGênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
are found within the Hox gene clusters. In mammals there are four Hox gene clusters, these contain five genes encoding miRNAs (mir-10a, mir-10b, mir-196a-1, mir-196a-2 and mir-196b). The mir-10a gene is located upstream of Hoxb4
HOXB4
Homeobox protein Hox-B4 is a protein that in humans is encoded by the HOXB4 gene....
and the mir-10b gene is located upstream of Hoxd4
HOXD4
Homeobox protein Hox-D4 is a protein that in humans is encoded by the HOXD4 gene.- External links :...
. Zebrafish have seven Hox gene clusters, genes encoding miR-10 (mir-10a, mir-10b-1, mir-10b-2 and mir-10c) are found in the Hox Ba, Bb, Ca and Da clusters. A fourth miR-10 gene (mir-10d) is found elsewhere in the genome, at a location homologous to the pufferfish HoxDd cluster.
miR-10*
A miRNA can be derived from the each arm of the pre-miRNA hairpin. The least common of these two miRNA products is denoted by the addition of * to the miRNA name. Both miR-10 and miR-10* have been detected in Drosophila. There are many potential targets for miR-10* in Drosophila, including several Hox genes, indicating that miR-10* may also be functional. In Drosophila most mature miR-10 sequences are produced from the 3' armDirectionality (molecular biology)
Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. The chemical convention of naming carbon atoms in the nucleotide sugar-ring numerically gives rise to a 5′-end and a 3′-end...
of the precursor while in the beetle Tribolium castaneum most production comes from the 5' arm
Directionality (molecular biology)
Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. The chemical convention of naming carbon atoms in the nucleotide sugar-ring numerically gives rise to a 5′-end and a 3′-end...
. These changes of arm preference during evolution are termed arm switching events, and they are relatively frequent during the evolution of microRNAs.
Pattern of expression
In adult animals, expression of miR-10 is limited to specific organs. The highest levels of miR-10a and miR-10b have been found in the kidneyKidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s of mice. Lower levels of miR-10a are seen in small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
and spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, and lower levels of miR-10b are seen in skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
. Expression of miR-10b has also been detected in the ovaries. Adult zebrafish express miR-10a in heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, testis and ovary, and miR-10b in muscle and liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
.
In developing embryos, miR-10 is detected at specific stages. Zebrafish embryos show miR-10a expression from 48 to 120 hours post-fertilisation
Fertilisation
Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
, and miR-10b expression from 12 to 120 hours post-fertilisation.
In Drosophila expression of miR-10-3p is highest in 12 to 24 hour old embryos and in 1st and 3rd instar
Instar
An instar is a developmental stage of arthropods, such as insects, between each molt , until sexual maturity is reached. Arthropods must shed the exoskeleton in order to grow or assume a new form. Differences between instars can often be seen in altered body proportions, colors, patterns, or...
larvae
Larvae
In Roman mythology, lemures were shades or spirits of the restless or malignant dead, and are probably cognate with an extended sense of larvae as disturbing or frightening...
. Levels of miR-10-5p are highest in 12 to 24 hour old embryos and much lower in larvae.
In stage 5 Drosophila embryos (130–180 minutes post-fertilisation), miR-10 is distributed throughout 50-80% of the length of the egg. Later in development miRNA-10 becomes localised into bands, and levels decrease by stage 7 (195–200 minutes post-fertilisation). miR10 reappears by stage 11 (320–440 minutes post-fertilisation), where it is found in the ventral nerve cord
Ventral nerve cord
The ventral nerve cord makes up the nervous system of some phyla of the invertebrates, particularly within the nematodes, annelids and the arthropods. It usually consists of cerebral ganglia anteriorly with the nerve cords running down the ventral plane of the organism...
, posterior midgut
Midgut
The midgut is the portion of the embryo from which most of the intestines develop. After it bends around the superior mesenteric artery, it is called the "midgut loop"...
and hindgut
Hindgut
The hindgut is the posterior part of the alimentary canal. In mammals, it includes the distal third of the transverse colon and the splenic flexure, the descending colon, sigmoid colon and rectum.-Blood flow:...
. At stage 14 (620–680 hours post-fertilisation), miRNA-10 is localised to the posterior midgut and the anal pad. In Drosophila larvae, miR-10-3p is found in the imaginal disc
Imaginal disc
An imaginal disc is one of the parts of a holometabolous insect larva that will become a portion of the outside of the adult insect during the pupal transformation. Contained within the body of the larva, there are pairs of discs that will form, for instance, the wings or legs or antennae or other...
s (groups of cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
which are destined to become adult structures upon metamorphosis
Metamorphosis
Metamorphosis is a biological process by which an animal physically develops after birth or hatching, involving a conspicuous and relatively abrupt change in the animal's body structure through cell growth and differentiation...
). Expression of miR-10ba in mouse embryos shows a similar pattern to that of the Hoxb4 gene. Highest levels are found in the posterior trunk of the embryo, surrounding the hindlimb buds
Limb bud
In embryology, the limb bud is a structure formed by the developing limb, derived from lateral plate mesoderm. It is intimately related with the apical ectodermal ridge, which secretes factors inducing the initial differentiation of the limb bud...
. Similarly, expression is restricted to the posterior trunk of chicken embryos. In Zebrafish embryos expression of miR-10 is also restricted to the posterior trunk, later in development it is further restricted to the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
.
Targets of miR-10
A number of Hox genes have been shown to be regulated by miR-10. These genes encode transcription factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s which are important in embryonic development. In zebrafish embryos, miR-10 binds to sites in the three prime untranslated region
Three prime untranslated region
In molecular genetics, the three prime untranslated region is a particular section of messenger RNA . It is preceeded by the coding region....
(3'UTR) of the HoxB1a and HoxB3a genes, which are important in anterior-posterior patterning during embryonic development. Binding of miR-10 leads to the repression
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
of these genes. It also acts synergistically
Synergy
Synergy may be defined as two or more things functioning together to produce a result not independently obtainable.The term synergy comes from the Greek word from , , meaning "working together".-Definitions and usages:...
with HoxB4 to repress these genes. The mir-10 gene is located near to the HoxB1a and HoxB3a genes within the zebrafish genome, Hox-1 and Hox-3 paralogues located on different Hox clusters are not targets of miR-10. Human HOXD10
HOXD10
Homeobox D10, also known as HOXD10, is a protein which in humans is encoded by the HOXD10 gene.- Function :This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2...
gene has also been shown experimentally to be repressed by miR-10a and miR-10b.
It has also been experimentally verified that miR-10a downregulates the human HOXA1 and HOXA3
HOXA3
Homeobox protein Hox-A3 is a protein that in humans is encoded by the HOXA3 gene.- Regulation :The HOXA3 gene is repressed by the microRNA miR-10a....
genes. Control of the Hox genes by miR-10 suggests that this microRNA may play an important role in development.
In addition to the Hox genes, miR-10a represses the transcription factor USF2
USF2
Upstream stimulatory factor 2 is a protein that in humans is encoded by the USF2 gene.-Interactions:USF2 has been shown to interact with USF1 , PPRC1 and BRCA1.- Regulation :The USF2 gene is repressed by the microRNA miR-10a....
and the Ran
Ran (biology)
Ran is a small 25Kda protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily....
and Pbp1 genes.
miR-10a binds to the five prime untranslated region
Five prime untranslated region
A messenger ribonucleic acid molecule codes for a protein through translation. The mRNA also contains regions that are not translated: in eukaryotes these include the 5' untranslated region, 3' untranslated region, 5' cap and poly-A tail....
(5'UTR) of mRNAs encoding ribosomal proteins, and increases their translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
. It binds immediately downstream of the 5' oligopyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
tract (5'TOP) motif, a region important in the regulation of ribosomal protein synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
.
Association with cancer
Recently there has been much interest in abnormal levels of expression of microRNAs in cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s. Upregulation of miR-10 has been found in a number of cancers. Increased levels of miR-10a have been found in glioblastoma
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...
, anaplastic astrocytoma
Anaplastic astrocytoma
-Symptoms:Initial presenting symptoms most commonly are headache, depressed mental status, focal neurological deficits, and/or seizures. The growth rate and mean interval between onset of symptoms and diagnosis is approximately 1.5–2 years but is highly variable, being intermediate between that of...
s, primary hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
s and colon cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
. Increased levels of miR-10b have been found in glioblastoma, anaplastic astrocytomas, pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
, and metastatic
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. Although high expression of miR-10b is found in metastatic breast cancers, it does not appear to be present at high levels in early breast cancers.
Downregulation of miR-10a has been found in chronic myeloid leukemia
Chronic myelogenous leukemia
Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...
. USF2, a target gene of miR-10a, has been found to be overexpressed in these leukemias. Downregulation of miR-10a has also been found in acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
, the most common acute leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
affecting adults. Conversely, miR-10a and miR-10b have found to be upregulated in acute myeloid leukemia with NPM1
NPM1
Nucleophosmin , also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.- Function :...
mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s; these account for approximately a third of adult acute myeloid leukemia cases and contain mutations in the NPM1 gene which result in the relocation of NPM1 from the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
to the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. Upregulation of miR-10b has also been found in B-cell chronic lymphocytic leukemia, the most common type of leukemia.
Genomic copy number abnormalities involving microRNA genes (both increases and decreases in copy number) have been found in cancers. A gain in copy number of the mir-10a gene has been found in melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and breast cancer.
Upstream of the mir-10b gene is a promoter region containing a binding site for the Twist transcription factor
Twist transcription factor
Twist transcription factor is a basic-helix-loop-helix transcription factor associated with Saethre-Chotzen syndrome.-Interactions:Twist transcription factor has been shown to interact with EP300, TCF3 and PCAF.-External links:*...
(Twist). Binding of Twist to this promoter region induces
Regulation of gene expression
Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...
miR-10b expression, leading to a reduced translation of the tumour suppressor
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
HOXD10. This results in upregulation of RhoA
RHOA
Ras homolog gene family, member A is a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers. In humans, it is encoded by the gene RHOA....
/RhoC
RhoC
RhoC is a small signaling G protein , and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC. -Mechanism and function:...
, Rho kinase
Rho-associated protein kinase
Rho-associated protein kinase is a kinase belonging to the AGC family of serine-threonine kinases. It is mainly involved in regulating the shape and movement of cells by acting on the cytoskeleton....
activation and tumour
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
cell invasion.
External links
- miRBase family MIPF0000033
- miRBase family MIPF0000025
- miRBase family MIPF0000268
- miRBase family MIPF0000271
- miRBase entry for human miR-10a
- miRBase entry for human miR-10b
- miRDB predicted targets for human miR-10a
- miRDB predicted targets for human miR-10b
- miRNAMap entry for human miR-10a
- miRNAMap entry for human miR-10b
- HNGC entry for miR-10a
- HGNC entry for miR-10b