Mir-10 microRNA precursor family

{{Short description|Short non-coding RNA gene}} {{Infobox rfam | Name = mir-10 | image = MiR-10_consensus_structure.jpg | width = 220px | caption = Conserved secondary structure of the mir-10 miRNA. Including marking up the mature miR and miR* sequences and corresponding seeds. | Symbol = miR-10 | AltSymbols = miR-51, miR-57, miR-99, miR-100 | Rfam = RF00104 | miRBase_family = MIPF0000033 | RNA_type = microRNA | Tax_domain = ''Eukaryota; Metazoa'' | HGNCid = 31497 | OMIM = 610173 }}

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.<ref>{{cite journal | vauthors = Lee RC, Ambros V | title = An extensive class of small RNAs in Caenorhabditis elegans | journal = Science | volume = 294 | issue = 5543 | pages = 862–4 | date = October 2001 | pmid = 11679672 | doi = 10.1126/science.1065329 | bibcode = 2001Sci...294..862L | s2cid = 33480585 }}</ref><ref>{{cite journal | vauthors = Ambros V | title = microRNAs: tiny regulators with great potential | journal = Cell | volume = 107 | issue = 7 | pages = 823–6 | date = December 2001 | pmid = 11779458 | doi = 10.1016/S0092-8674(01)00616-X | doi-access = free }}</ref> ([https://web.archive.org/web/20070929111222/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_summary.pl?fam=MIPF0000033 MIPF0000033], [https://web.archive.org/web/20070926215636/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_summary.pl?fam=MIPF0000025 MIPF0000025]) miR-51 and miR-57 have currently only been identified in the nematode ''Caenorhabditis elegans'' ([https://web.archive.org/web/20070929083615/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_summary.pl?fam=MIPF0000268 MIPF0000268], [https://web.archive.org/web/20070929083350/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_summary.pl?fam=MIPF0000271 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.

== Species distribution == The presence of miR-10 has been detected in a diverse range of bilaterian animals. It is one of the most widely distributed 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''), gray 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''.<ref name="pmid20347954">{{cite journal | vauthors = Li SC, Chan WC, Hu LY, Lai CH, Hsu CN, Lin WC | title = Identification of homologous microRNAs in 56 animal genomes | journal = Genomics | volume = 96 | issue = 1 | pages = 1–9 | date = July 2010 | pmid = 20347954 | doi = 10.1016/j.ygeno.2010.03.009 | doi-access = }}</ref><ref name="pmid17103184">{{cite journal | vauthors = Prochnik SE, Rokhsar DS, Aboobaker AA | title = Evidence for a microRNA expansion in the bilaterian ancestor | journal = Development Genes and Evolution | volume = 217 | issue = 1 | pages = 73–7 | date = January 2007 | pmid = 17103184 | doi = 10.1007/s00427-006-0116-1 | s2cid = 6192333 }}</ref><ref name="pmid19997615">{{cite journal | vauthors = Huang J, Hao P, Chen H, Hu W, Yan Q, Liu F, Han ZG | title = Genome-wide identification of Schistosoma japonicum microRNAs using a deep-sequencing approach | journal = PLOS ONE | volume = 4 | issue = 12 | article-number = e8206 | date = December 2009 | pmid = 19997615 | pmc = 2785426 | doi = 10.1371/journal.pone.0008206 | editor1-last = Diemert | editor1-first = David Joseph | bibcode = 2009PLoSO...4.8206H | doi-access = free }}</ref><ref name="pmid15361871">{{cite journal | vauthors = Mansfield JH, Harfe BD, Nissen R, Obenauer J, Srineel J, Chaudhuri A, Farzan-Kashani R, Zuker M, Pasquinelli AE, Ruvkun G, Sharp PA, Tabin CJ, McManus MT | title = MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression | journal = Nature Genetics | volume = 36 | issue = 10 | pages = 1079–83 | date = October 2004 | pmid = 15361871 | doi = 10.1038/ng1421 | doi-access = free }}</ref><ref name="pmid1370382">{{cite journal | vauthors = Teramura M, Kobayashi S, Hoshino S, Oshimi K, Mizoguchi H | title = Interleukin-11 enhances human megakaryocytopoiesis in vitro | journal = Blood | volume = 79 | issue = 2 | pages = 327–31 | date = January 1992 | pmid = 1370382 | doi = 10.1182/blood.V79.2.327.327 | doi-access = free }}</ref><ref name="pmid17355992">{{cite journal | vauthors = Beuvink I, Kolb FA, Budach W, Garnier A, Lange J, Natt F, Dengler U, Hall J, Filipowicz W, Weiler J | title = A novel microarray approach reveals new tissue-specific signatures of known and predicted mammalian microRNAs | journal = Nucleic Acids Research | volume = 35 | issue = 7 | pages = e52 | year = 2007 | pmid = 17355992 | pmc = 1874652 | doi = 10.1093/nar/gkl1118 }}</ref> 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'' genes 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''.<ref name="pmid19461655">{{cite journal | vauthors = Lund AH | title = miR-10 in development and cancer | journal = Cell Death and Differentiation | volume = 17 | issue = 2 | pages = 209–14 | date = February 2010 | pmid = 19461655 | doi = 10.1038/cdd.2009.58 | doi-access = free }}</ref> 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.<ref name="pmid16736008">{{cite journal | vauthors = Woltering JM, Durston AJ | title = The zebrafish hoxDb cluster has been reduced to a single microRNA | journal = Nature Genetics | volume = 38 | issue = 6 | pages = 601–2 | date = June 2006 | pmid = 16736008 | doi = 10.1038/ng0606-601 | s2cid = 41211603 }}</ref>

== miR-10* == A miRNA can be derived from each arm of the pre-miRNA hairpin. Historically, the least common of these two miRNA products was denoted by the addition of * to the miRNA name, however the modern convention is to denote mature miRNA products as 5p or 3p.<ref name="urlmiRBase::Sequences">{{cite web |url=https://www.mirbase.org/help/# |title=miRBase }}</ref> 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.<ref name="pmid17989254">{{cite journal | vauthors = Ruby JG, Stark A, Johnston WK, Kellis M, Bartel DP, Lai EC | title = Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs | journal = Genome Research | volume = 17 | issue = 12 | pages = 1850–64 | date = December 2007 | pmid = 17989254 | pmc = 2099593 | doi = 10.1101/gr.6597907 }}</ref><ref name="pmid17989255">{{cite journal | vauthors = Stark A, Kheradpour P, Parts L, Brennecke J, Hodges E, Hannon GJ, Kellis M | title = Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes | journal = Genome Research | volume = 17 | issue = 12 | pages = 1865–79 | date = December 2007 | pmid = 17989255 | pmc = 2099594 | doi = 10.1101/gr.6593807 }}</ref> In ''Drosophila'' most mature miR-10 sequences are produced from the 3' arm of the precursor while in the beetle ''Tribolium castaneum'' most production comes from the 5' arm.<ref name="pmid21212805">{{cite journal | vauthors = Griffiths-Jones S, Hui JH, Marco A, Ronshaugen M | title = MicroRNA evolution by arm switching | journal = EMBO Reports | volume = 12 | issue = 2 | pages = 172–7 | date = February 2011 | pmid = 21212805 | pmc = 3049427 | doi = 10.1038/embor.2010.191 }}</ref> These changes of arm preference during evolution are termed arm switching events, and they are relatively frequent during the evolution of microRNAs.<ref name="pmid21212805" /><ref name="pmid20817720">{{cite journal | vauthors = Marco A, Hui JH, Ronshaugen M, Griffiths-Jones S | title = Functional shifts in insect microRNA evolution | journal = Genome Biology and Evolution | volume = 2 | pages = 686–96 | year = 2010 | pmid = 20817720 | pmc = 2956262 | doi = 10.1093/gbe/evq053 }}</ref>

== 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 kidneys 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.<ref name="pmid1370382"/><ref name="pmid17355992"/><ref name="pmid17604727">{{cite journal | vauthors = Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foà R, Schliwka J, Fuchs U, Novosel A, Müller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T | title = A mammalian microRNA expression atlas based on small RNA library sequencing | journal = Cell | volume = 129 | issue = 7 | pages = 1401–14 | date = June 2007 | pmid = 17604727 | pmc = 2681231 | doi = 10.1016/j.cell.2007.04.040 }}</ref> Adult zebrafish express miR-10a in heart, testis and ovary, and miR-10b in muscle and liver.<ref name="pmid15919954">{{cite journal | vauthors = Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S, Plasterk RH | title = MicroRNA expression in zebrafish embryonic development | journal = Science | volume = 309 | issue = 5732 | pages = 310–1 | date = July 2005 | pmid = 15919954 | pmc = <!-- This article has exactly 9 authors --> | doi = 10.1126/science.1114519 | bibcode = 2005Sci...309..310W }}</ref>

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.<ref name="pmid15919954" /> 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.<ref name="pmid17989254"/>

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.<ref name="pmid16330759">{{cite journal | vauthors = Aboobaker AA, Tomancak P, Patel N, Rubin GM, Lai EC | title = Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 50 | pages = 18017–22 | date = December 2005 | pmid = 16330759 | pmc = 1306796 | doi = 10.1073/pnas.0508823102 | bibcode = 2005PNAS..10218017A | doi-access = free }}</ref> In ''Drosophila'' larvae, miR-10-3p is found in the imaginal discs (groups of cells which are destined to become adult structures upon metamorphosis).<ref name="pmid17989254" /> 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.<ref name="pmid15361871"/> 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.<ref name="pmid15919954" />

== Targets of miR-10 == A number of Hox genes have been shown to be regulated by miR-10. These genes encode transcription factors 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.<ref name="pmid18167555">{{cite journal | vauthors = Woltering JM, Durston AJ | title = MiR-10 represses HoxB1a and HoxB3a in zebrafish | journal = PLOS ONE | volume = 3 | issue = 1 | article-number = e1396 | date = January 2008 | pmid = 18167555 | pmc = 2148072 | doi = 10.1371/journal.pone.0001396 | editor1-last = Raible | editor1-first = David | bibcode = 2008PLoSO...3.1396W | doi-access = free }}</ref> Human ''HOXD10'' gene has also been shown experimentally to be repressed by miR-10a and miR-10b.<ref name="pmid19461655" /><ref name="pmid17898713">{{cite journal | vauthors = Ma L, Teruya-Feldstein J, Weinberg RA | title = Tumour invasion and metastasis initiated by microRNA-10b in breast cancer | journal = Nature | volume = 449 | issue = 7163 | pages = 682–8 | date = October 2007 | pmid = 17898713 | doi = 10.1038/nature06174 | bibcode = 2007Natur.449..682M | s2cid = 4421050 }}</ref><ref name="pmid17660710">{{cite journal | vauthors = Han L, Witmer PD, Casey E, Valle D, Sukumar S | title = DNA methylation regulates MicroRNA expression | journal = Cancer Biology & Therapy | volume = 6 | issue = 8 | pages = 1284–8 | date = August 2007 | pmid = 17660710 | doi = 10.4161/cbt.6.8.4486 | doi-access = free }}</ref>

It has also been experimentally verified that miR-10a downregulates the human ''HOXA1'' and ''HOXA3'' genes.<ref name="pmid17660710" /><ref name="pmid16549775">{{cite journal | vauthors = Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R, Volinia S, Bhatt D, Alder H, Marcucci G, Calin GA, Liu CG, Bloomfield CD, Andreeff M, Croce CM | title = MicroRNA fingerprints during human megakaryocytopoiesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 13 | pages = 5078–83 | date = March 2006 | pmid = 16549775 | pmc = 1458797 | doi = 10.1073/pnas.0600587103 | bibcode = 2006PNAS..103.5078G | doi-access = free }}</ref> Control of the Hox genes by miR-10 suggests that this microRNA may play an important role in development.<ref name="pmid19461655" />

In addition to the Hox genes, miR-10a represses the transcription factor ''USF2'' and the ''Ran'' and ''Pbp1'' genes.<ref name="pmid18498749">{{cite journal | vauthors = Ørom UA, Nielsen FC, Lund AH | title = MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation | journal = Molecular Cell | volume = 30 | issue = 4 | pages = 460–71 | date = May 2008 | pmid = 18498749 | doi = 10.1016/j.molcel.2008.05.001 | doi-access = free }}</ref><ref name="pmid19074828">{{cite journal | vauthors = Agirre X, Jiménez-Velasco A, San José-Enériz E, Garate L, Bandrés E, Cordeu L, Aparicio O, Saez B, Navarro G, Vilas-Zornoza A, Pérez-Roger I, García-Foncillas J, Torres A, Heiniger A, Calasanz MJ, Fortes P, Román-Gómez J, Prósper F | title = Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth | journal = Molecular Cancer Research | volume = 6 | issue = 12 | pages = 1830–40 | date = December 2008 | pmid = 19074828 | doi = 10.1158/1541-7786.MCR-08-0167 | doi-access = free | hdl = 10171/17940 | hdl-access = free }}</ref> The cell-surface proteoglycan Syndecan-1 is a target of miR-10b.<ref>{{cite journal |last1=Ibrahim |first1=Sherif |title=Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a Rho-GTPase- and E-cadherin-dependent mechanism. |journal=International Journal of Cancer |date=15 September 2012 |volume=131 |issue=6 |pages=E884-96 |doi=10.1002/ijc.27629 |pmid=22573479|s2cid=42359653 }}</ref><ref>{{cite journal | vauthors = Schneider C, Kässens N, Greve B, Hassan H, Schüring AN, Starzinski-Powitz A, Kiesel L, Seidler DG, Götte M | title = Targeting of syndecan-1 by micro-ribonucleic acid miR-10b modulates invasiveness of endometriotic cells via dysregulation of the proteolytic milieu and interleukin-6 secretion | journal = Fertility and Sterility | volume = 99 | issue = 3 | pages = 871–881.e1 | date = March 2013 | pmid = 23206733 | doi = 10.1016/j.fertnstert.2012.10.051 | doi-access = free }}</ref>

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.<ref name="pmid18498749" />

== Association with cancer == Recently there has been much interest in abnormal levels of expression of microRNAs in cancers. Upregulation of miR-10 has been found in a number of cancers. Increased levels of miR-10a have been found in glioblastoma, anaplastic astrocytomas, primary hepatocellular carcinomas and colon cancer. Increased levels of miR-10b have been found in glioblastoma, anaplastic astrocytomas, pancreatic cancer, and metastatic breast cancer.<ref name="pmid19461655" /><ref name="pmid17898713" /> 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.<ref name="pmid17898713" /><ref name="pmid18948893">{{cite journal | vauthors = Gee HE, Camps C, Buffa FM, Colella S, Sheldon H, Gleadle JM, Ragoussis J, Harris AL | title = MicroRNA-10b and breast cancer metastasis | journal = Nature | volume = 455 | issue = 7216 | pages = E8–9; author reply E9 | date = October 2008 | pmid = 18948893 | doi = 10.1038/nature07362 | bibcode = 2008Natur.455....8G | s2cid = 205215012 }}</ref> The expression of miR-10b is correlated with overall survival in 1262 breast cancer patients.<ref>{{cite journal | vauthors = Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B | title = miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients | journal = Breast Cancer Research and Treatment | volume = 160 | issue = 3 | pages = 439–446 | date = December 2016 | pmid = 27744485 | doi = 10.1007/s10549-016-4013-7 | s2cid = 11165696 }}</ref>

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.<ref name="pmid19074828" /> Downregulation of miR-10a has also been found in acute myeloid leukemia, the most common acute leukemia affecting adults.<ref name="pmid18337557">{{cite journal | vauthors = Jongen-Lavrencic M, Sun SM, Dijkstra MK, Valk PJ, Löwenberg B | title = MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia | journal = Blood | volume = 111 | issue = 10 | pages = 5078–85 | date = May 2008 | pmid = 18337557 | doi = 10.1182/blood-2008-01-133355 | doi-access = | hdl = 1765/29105 | hdl-access = free }}</ref> Conversely, miR-10a and miR-10b have found to be upregulated in acute myeloid leukemia with ''NPM1'' mutations; 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.<ref name="pmid18308931">{{cite journal | vauthors = Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T, Liso A, Diverio D, Mancini M, Meloni G, Foa R, Martelli MF, Mecucci C, Croce CM, Falini B | title = Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 10 | pages = 3945–50 | date = March 2008 | pmid = 18308931 | pmc = 2268779 | doi = 10.1073/pnas.0800135105 | bibcode = 2008PNAS..105.3945G | doi-access = free }}</ref> Upregulation of miR-10b has also been found in B-cell chronic lymphocytic leukemia, the most common type of leukemia.<ref name="pmid15284443">{{cite journal | vauthors = Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM | title = MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 32 | pages = 11755–60 | date = August 2004 | pmid = 15284443 | pmc = 511048 | doi = 10.1073/pnas.0404432101 | bibcode = 2004PNAS..10111755C | doi-access = free }}</ref>

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.<ref name="pmid16754881">{{cite journal | vauthors = Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, Liang S, Naylor TL, Barchetti A, Ward MR, Yao G, Medina A, O'brien-Jenkins A, Katsaros D, Hatzigeorgiou A, Gimotty PA, Weber BL, Coukos G | title = microRNAs exhibit high frequency genomic alterations in human cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 24 | pages = 9136–41 | date = June 2006 | pmid = 16754881 | pmc = 1474008 | doi = 10.1073/pnas.0508889103 | bibcode = 2006PNAS..103.9136Z | doi-access = free }}</ref>

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.<ref name="pmid17898713" /><ref name="pmid20843787">{{cite journal | vauthors = Bourguignon LY, Wong G, Earle C, Krueger K, Spevak CC | title = Hyaluronan-CD44 interaction promotes c-Src-mediated twist signaling, microRNA-10b expression, and RhoA/RhoC up-regulation, leading to Rho-kinase-associated cytoskeleton activation and breast tumor cell invasion | journal = The Journal of Biological Chemistry | volume = 285 | issue = 47 | pages = 36721–35 | date = November 2010 | pmid = 20843787 | pmc = 2978601 | doi = 10.1074/jbc.M110.162305 | doi-access = free }}</ref>

===Studies in metastatic tumors===

Boston, Massachusetts-based Transcode Therapeutics is developing drugs to target Mir-10b, which the company regards as "a master regulator of metastatic disease".<ref name="Therapeutics 2024 l060">{{cite web | last=Therapeutics | first=TransCode | title=TransCode Therapeutics To Present At 2024 RNA Leaders Europe Congress | website=WDTN.com | date=6 Mar 2024 | url=https://www.wdtn.com/business/press-releases/globenewswire/9059275/transcode-therapeutics-to-present-at-2024-rna-leaders-europe-congress/ | access-date=8 Mar 2024}}</ref> Preclinical trials in a murine model of metastatic breast cancer found that one of their drugs candidates, MN-anti-miR10b (now known as TTX-MC138), combined with low-dose doxorubicin, resulted in a complete elimination of distant metastases in 65% of the rodents and a significant decrease in mortality.<ref name="Yoo Kavishwar Wang Ross 2017 p. ">{{cite journal | last1=Yoo | first1=Byunghee | last2=Kavishwar | first2=Amol | last3=Wang | first3=Ping | last4=Ross | first4=Alana | last5=Pantazopoulos | first5=Pamela | last6=Dudley | first6=Michael | last7=Moore | first7=Anna | last8=Medarova | first8=Zdravka | title=Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer | journal=Scientific Reports | publisher=Springer Science and Business Media LLC | volume=7 | issue=1 | date=21 Mar 2017 | issn=2045-2322 | doi=10.1038/srep45060 | article-number=45060| pmid=28322342 | pmc=5359550 | bibcode=2017NatSR...745060Y }}</ref> A first-in-human phase 0 study of TTX-MC138 began in 2023. The company believes the drug, and others with similar mechanisms, could dramatically increase survival rates for people with metastatic tumors.<ref name="BioSpace 2023 o320">{{cite web | title=TransCode Therapeutics Announces First Subject Dosed with Radiolabeled TTX-MC138 in First-In-Human Clinical TrialDesigned to demonstrate delivery of TTX-MC138 to metastatic lesions | website=BioSpace | date=23 Aug 2023 | url=https://www.biospace.com/article/releases/transcode-therapeutics-announces-first-subject-dosed-with-radiolabeled-ttx-mc138-in-first-in-human-clinical-trialdesigned-to-demonstrate-delivery-of-ttx-mc138-to-metastatic-lesions/ | access-date=8 Mar 2024}}</ref>

== See also == * MicroRNA * Gene expression * Hox genes

== References == {{reflist|30em}}

== Further reading == {{refbegin}} * {{cite journal | vauthors = Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T | title = Identification of novel genes coding for small expressed RNAs | journal = Science | volume = 294 | issue = 5543 | pages = 853–8 | date = October 2001 | pmid = 11679670 | doi = 10.1126/science.1064921 | hdl = 11858/00-001M-0000-0012-F65F-2 | bibcode = 2001Sci...294..853L | s2cid = 18101169 | hdl-access = free }} * {{cite journal | vauthors = Izzotti A, Calin GA, Arrigo P, Steele VE, Croce CM, De Flora S | title = Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke | journal = FASEB Journal | volume = 23 | issue = 3 | pages = 806–12 | date = March 2009 | pmid = 18952709 | pmc = 2653990 | doi = 10.1096/fj.08-121384 | doi-access = free }} * {{cite journal | vauthors = Chen Z, Jin Y, Yu D, Wang A, Mahjabeen I, Wang C, Liu X, Zhou X | title = Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma | journal = Oral Oncology | volume = 48 | issue = 8 | pages = 686–91 | date = August 2012 | pmid = 22425712 | pmc = 3380146 | doi = 10.1016/j.oraloncology.2012.02.020 }} {{refend}}

== External links ==

{{div col|colwidth=30em}} * {{Rfam|id=RF00104|name=mir-10 microRNA precursor family}} * {{miRBase|id=MIPF0000033|name=mir-10}} * {{miRBase|id=MIPF0000025|name=mir-99}} * {{miRBase|id=MIPF0000268|name=mir-51}} * {{miRBase|id=MIPF0000271|name=mir-57}} * [http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MIMAT0000253 miRBase entry for human miR-10a] * [http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MIMAT0000254 miRBase entry for human miR-10b] * [http://mirdb.org/cgi-bin/search.cgi?searchType=miRNA&searchBox=hsa-miR-10a&full=1 miRDB predicted targets for human miR-10a] * [http://mirdb.org/cgi-bin/search.cgi?searchType=miRNA&searchBox=hsa-miR-10b&full=1 miRDB predicted targets for human miR-10b] * [http://mirnamap.mbc.nctu.edu.tw/php/mirna_entry.php?acc=MI0000266 miRNAMap entry for human miR-10a] * [http://mirnamap.mbc.nctu.edu.tw/php/mirna_entry.php?acc=MI0000267 miRNAMap entry for human miR-10b] * [https://www.genenames.org/data/hgnc_data.php?hgnc_id=HGNC:31497 HNGC entry for miR-10a] * [https://www.genenames.org/data/hgnc_data.php?hgnc_id=HGNC:31498 HGNC entry for miR-10b] {{div col end}} {{miRNA precursor families}}

{{DEFAULTSORT:Mir-10 Microrna Precursor Family}} Category:MicroRNA Category:MicroRNA precursor families