View source for MiR-138

{{Infobox rfam
| Name = miR-138
| image = Mir-138_SS.png
| width =
| caption = Conserved secondary structure of miR-138 prescursor
| Symbol = miR-138
| AltSymbols =
| Rfam = RF00671
| miRBase = MI0000476
| miRBase_family = MIPF0000075
| RNA_type = miRNA
| Tax_domain = [[Animalia]]
| GO =
| SO =
| CAS_number =
| EntrezGene = 406929
| HGNCid = 31524
| OMIM =
| PDB =
| RefSeq =
| Chromosome = 3
| Arm = p
| Band =
| LocusSupplementaryData =
}} {{lowercase}}
'''miR-138''' is a family of [[microRNA]] precursors found in animals, including [[human]]s.<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 | display-authors = 6  | title = A mammalian microRNA expression atlas based on small RNA library sequencing | journal = Cell | volume = 129 | issue = 7 | pages = 1401–14 | date = Jun 2007 | pmid = 17604727 | pmc = 2681231 | doi = 10.1016/j.cell.2007.04.040 }}</ref> MicroRNAs are typically transcribed as ~70 [[nucleotide]] precursors and subsequently processed by the [[Dicer]] enzyme to give a ~22 nucleotide product.<ref name="PMID11779458">{{cite journal | vauthors = Ambros V | title = microRNAs: tiny regulators with great potential | journal = Cell | volume = 107 | issue = 7 | pages = 823–6 | date = Dec 2001 | pmid = 11779458 | doi = 10.1016/S0092-8674(01)00616-X }}</ref> The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138.

miR-138 has been used as an example of the [[post-transcriptional regulation]] of miRNA, due to the finding that while the precursor is expressed ubiquitously, the mature product is found only in specific [[cell type]]s.<ref name="PMID16738409">{{cite journal | vauthors = Obernosterer G, Leuschner PJ, Alenius M, Martinez J | title = Post-transcriptional regulation of microRNA expression | journal = RNA | volume = 12 | issue = 7 | pages = 1161–7 | date = Jul 2006 | pmid = 16738409 | pmc = 1484437 | doi = 10.1261/rna.2322506 }}</ref>

== Species distribution ==
The presence of miR-138 has been detected experimentally in humans (''Homo sapiens'')<ref name="PMID17604727" /><ref name="PMID12007417">{{cite journal | vauthors = Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T | title = Identification of tissue-specific microRNAs from mouse | journal = Current Biology | volume = 12 | issue = 9 | pages = 735–9 | date = Apr 2002 | pmid = 12007417 | doi = 10.1016/s0960-9822(02)00809-6 }}</ref><ref name="PMID17616659">{{cite journal | vauthors = Lui WO, Pourmand N, Patterson BK, Fire A | title = Patterns of known and novel small RNAs in human cervical cancer | journal = Cancer Research | volume = 67 | issue = 13 | pages = 6031–43 | date = Jul 2007 | pmid = 17616659 | doi = 10.1158/0008-5472.can-06-0561 }}</ref> and in different animals including [[house mouse]] (''Mus musculus''),<ref name=PMID17604727 /><ref name=PMID16738409 /><ref name="PMID12007417" /><ref name="PMID15634332">{{cite journal | vauthors = Weber MJ | title = New human and mouse microRNA genes found by homology search | journal = The FEBS Journal | volume = 272 | issue = 1 | pages = 59–73 | date = Jan 2005 | pmid = 15634332 | doi = 10.1111/j.1432-1033.2004.04389.x }}</ref><ref name="PMID14691248">{{cite journal | vauthors = Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM, Ruvkun G | title = Identification of many microRNAs that copurify with polyribosomes in mammalian neurons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 1 | pages = 360–5 | date = Jan 2004 | pmid = 14691248 | pmc = 314190 | doi = 10.1073/pnas.2333854100 }}</ref><ref name=PMID20215419>{{cite journal | vauthors = Ahn HW, Morin RD, Zhao H, Harris RA, Coarfa C, Chen ZJ, Milosavljevic A, Marra MA, Rajkovic A | title = MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing | journal = Molecular Human Reproduction | volume = 16 | issue = 7 | pages = 463–71 | date = Jul 2010 | pmid = 20215419 | pmc = 2882868 | doi = 10.1093/molehr/gaq017 }}</ref><ref name=PMID20413612>{{cite journal | vauthors = Chiang HR, Schoenfeld LW, Ruby JG, Auyeung VC, Spies N, Baek D, Johnston WK, Russ C, Luo S, Babiarz JE, Blelloch R, Schroth GP, Nusbaum C, Bartel DP | title = Mammalian microRNAs: experimental evaluation of novel and previously annotated genes | journal = Genes & Development | volume = 24 | issue = 10 | pages = 992–1009 | date = May 2010 | pmid = 20413612 | doi = 10.1101/gad.1884710 | pmc=2867214}}</ref> [[brown rat]] (''Rattus norvegicus''),<ref name="PMID17604727" /><ref name="PMID14691248" /><ref name=PMID15345052>{{cite journal | vauthors = Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P, Constantine-Paton M, Horvitz HR | title = Microarray analysis of microRNA expression in the developing mammalian brain | journal = Genome Biology | volume = 5 | issue = 9 | pages = R68 | date = 2004 | pmid = 15345052 | doi = 10.1186/gb-2004-5-9-r68 | pmc=522875}}</ref><ref name=PMID17805466>{{cite journal | vauthors = He X, Zhang Q, Liu Y, Pan X | title = Cloning and identification of novel microRNAs from rat hippocampus | journal = Acta Biochimica et Biophysica Sinica | volume = 39 | issue = 9 | pages = 708–14 | date = Sep 2007 | pmid = 17805466 | doi = 10.1111/j.1745-7270.2007.00324.x }}</ref><ref name=PMID20403161>{{cite journal | vauthors = Linsen SE, de Wit E, de Bruijn E, Cuppen E | title = Small RNA expression and strain specificity in the rat | journal = BMC Genomics | volume = 11 | issue = 1 | pages = 249 | date = 19 April 2010 | pmid = 20403161 | pmc = 2864251 | doi = 10.1186/1471-2164-11-249 }}</ref> [[platypus]] (''Ornithorhynchus anatinus''),<ref name=PMID18463306>{{cite journal | vauthors = Murchison EP, Kheradpour P, Sachidanandam R, Smith C, Hodges E, Xuan Z, Kellis M, Grützner F, Stark A, Hannon GJ | title = Conservation of small RNA pathways in platypus | journal = Genome Research | volume = 18 | issue = 6 | pages = 995–1004 | date = Jun 2008 | pmid = 18463306 | pmc = 2413167 | doi = 10.1101/gr.073056.107 }}</ref> [[Carolina anole]](''Anolis carolinensis''),<ref name=PMID21775315>{{cite journal | vauthors = Lyson TR, Sperling EA, Heimberg AM, Gauthier JA, King BL, Peterson KJ | title = MicroRNAs support a turtle + lizard clade | journal = Biology Letters | volume = 8 | issue = 1 | pages = 104–7 | date = Feb 2012 | pmid = 21775315 | pmc = 3259949 | doi = 10.1098/rsbl.2011.0477 }}</ref> [[cattle]] (''Bos taurus''),<ref name="PMID17105755">{{cite journal | vauthors = Coutinho LL, Matukumalli LK, Sonstegard TS, Van Tassell CP, Gasbarre LC, Capuco AV, Smith TP | title = Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues | journal = Physiological Genomics | volume = 29 | issue = 1 | pages = 35–43 | date = Mar 2007 | pmid = 17105755 | doi = 10.1152/physiolgenomics.00081.2006 }}</ref><ref name="PMID19170227">{{cite journal | vauthors = Tesfaye D, Worku D, Rings F, Phatsara C, Tholen E, Schellander K, Hoelker M | title = Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach | journal = Molecular Reproduction and Development | volume = 76 | issue = 7 | pages = 665–77 | date = Jul 2009 | pmid = 19170227 | doi = 10.1002/mrd.21005 }}</ref> [[common carp]] (''Cyprinus carpio''),<ref name=PMID22303472>{{cite journal | vauthors = Yan X, Ding L, Li Y, Zhang X, Liang Y, Sun X, Teng CB | title = Identification and profiling of microRNAs from skeletal muscle of the common carp | journal = PLOS ONE | volume = 7 | issue = 1 | pages = e30925 | date = 2012 | pmid = 22303472 | pmc = 3267759 | doi = 10.1371/journal.pone.0030925 }}</ref> [[dog]] (''Canis familiaris''),<ref>{{cite journal | vauthors = Friedländer MR, Chen W, Adamidi C, Maaskola J, Einspanier R, Knespel S, Rajewsky N | title = Discovering microRNAs from deep sequencing data using miRDeep | journal = Nature Biotechnology | volume = 26 | issue = 4 | pages = 407–15 | date = Apr 2008 | pmid = 18392026 | doi = 10.1038/nbt1394 }}</ref> [[Chinese hamster]] (''Cricetulus griseus''),<ref name=PMID21392545>{{cite journal | vauthors = Hackl M, Jakobi T, Blom J, Doppmeier D, Brinkrolf K, Szczepanowski R, Bernhart SH, Höner Zu Siederdissen C, Bort JA, Wieser M, Kunert R, Jeffs S, Hofacker IL, Goesmann A, Pühler A, Borth N, Grillari J | title = Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering | journal = Journal of Biotechnology | volume = 153 | issue = 1–2 | pages = 62–75 | date = Apr 2011 | pmid = 21392545 | pmc = 3119918 | doi = 10.1016/j.jbiotec.2011.02.011 }}</ref> [[zebrafish]] (''Danio rerio''),<ref name=PMID15937218>{{cite journal | vauthors = Chen PY, Manninga H, Slanchev K, Chien M, Russo JJ, Ju J, Sheridan R, John B, Marks DS, Gaidatzis D, Sander C, Zavolan M, Tuschl T | title = The developmental miRNA profiles of zebrafish as determined by small RNA cloning | journal = Genes & Development | volume = 19 | issue = 11 | pages = 1288–93 | date = Jun 2005 | pmid = 15937218 | pmc = 1142552 | doi = 10.1101/gad.1310605 }}</ref> [[red junglefowl]] (''Gallus gallus''),<ref name=PMID15592404>{{cite journal | vauthors =  | title = Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution | journal = Nature | volume = 432 | issue = 7018 | pages = 695–716 | date = Dec 2004 | pmid = 15592404 | doi = 10.1038/nature03154 }}</ref> [[western gorilla]] (''Gorilla gorilla''),<ref name=PMID22453055>{{cite journal | vauthors = Dannemann M, Nickel B, Lizano E, Burbano HA, Kelso J | title = Annotation of primate miRNAs by high throughput sequencing of small RNA libraries | journal = BMC Genomics | volume = 13 | issue = 1 | pages = 116 | date = 27 March 2012 | pmid = 22453055 | doi = 10.1186/1471-2164-13-116 | pmc=3328248}}</ref> [[gray short-tailed opossum]] (''Monodelphis domestica''),<ref name=PMID17965199>{{cite journal | vauthors = Devor EJ, Samollow PB | title = In vitro and in silico annotation of conserved and nonconserved microRNAs in the genome of the marsupial Monodelphis domestica | journal = The Journal of Heredity | volume = 99 | issue = 1 | pages = 66–72 | date = January–February 2008 | pmid = 17965199 | doi = 10.1093/jhered/esm085 }}</ref> ''[[Oryzias latipes]]'',<ref name=PMID21143817>{{cite journal | vauthors = Li SC, Chan WC, Ho MR, Tsai KW, Hu LY, Lai CH, Hsu CN, Hwang PP, Lin WC | title = Discovery and characterization of medaka miRNA genes by next generation sequencing platform | journal = BMC Genomics | volume = 11 Suppl 4 | issue = Suppl 4 | pages = S8 | date = 2 December 2010 | pmid = 21143817 | pmc = 3005926 | doi = 10.1186/1471-2164-11-s4-s8 }}</ref> [[sea lamprey]] (''Petromyzon marinus''),<ref name=PMID20959416>{{cite journal | vauthors = Heimberg AM, Cowper-Sal-lari R, Sémon M, Donoghue PC, Peterson KJ | title = microRNAs reveal the interrelationships of hagfish, lampreys, and gnathostomes and the nature of the ancestral vertebrate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 45 | pages = 19379–83 | date = Nov 2010 | pmid = 20959416 | pmc = 2984222 | doi = 10.1073/pnas.1010350107 }}</ref> [[Tasmanian devil]] (''Sarcophilus harrisii''),<ref name=PMID20044575>{{cite journal | vauthors = Murchison EP, Tovar C, Hsu A, Bender HS, Kheradpour P, Rebbeck CA, Obendorf D, Conlan C, Bahlo M, Blizzard CA, Pyecroft S, Kreiss A, Kellis M, Stark A, Harkins TT, Marshall Graves JA, Woods GM, Hannon GJ, Papenfuss AT | title = The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer | journal = Science | volume = 327 | issue = 5961 | pages = 84–7 | date = Jan 2010 | pmid = 20044575 | pmc = 2982769 | doi = 10.1126/science.1180616 }}</ref> [[wild boar]] (''Sus scrofa'')<ref name=PMID21312241>{{cite journal | vauthors = Li G, Li Y, Li X, Ning X, Li M, Yang G | title = MicroRNA identity and abundance in developing swine adipose tissue as determined by Solexa sequencing | journal = Journal of Cellular Biochemistry | volume = 112 | issue = 5 | pages = 1318–28 | date = May 2011 | pmid = 21312241 | doi = 10.1002/jcb.23045 }}</ref> and [[zebra finch]] (''Taeniopygia guttata'').<ref name=PMID20360741>{{cite journal | vauthors = Warren WC, Clayton DF, Ellegren H, Arnold AP, Hillier LW, Künstner A, Searle S, White S, Vilella AJ, Fairley S, Heger A, Kong L, Ponting CP, Jarvis ED, Mello CV, Minx P, Lovell P, Velho TA, Ferris M, Balakrishnan CN, Sinha S, Blatti C, London SE, Li Y, Lin YC, George J, Sweedler J, Southey B, Gunaratne P, Watson M, Nam K, Backström N, Smeds L, Nabholz B, Itoh Y, Whitney O, Pfenning AR, Howard J, Völker M, Skinner BM, Griffin DK, Ye L, McLaren WM, Flicek P, Quesada V, Velasco G, Lopez-Otin C, Puente XS, Olender T, Lancet D, Smit AF, Hubley R, Konkel MK, Walker JA, Batzer MA, Gu W, Pollock DD, Chen L, Cheng Z, Eichler EE, Stapley J, Slate J, Ekblom R, Birkhead T, Burke T, Burt D, Scharff C, Adam I, Richard H, Sultan M, Soldatov A, Lehrach H, Edwards SV, Yang SP, Li X, Graves T, Fulton L, Nelson J, Chinwalla A, Hou S, Mardis ER, Wilson RK | display-authors = 6 | title = The genome of a songbird | journal = Nature | volume = 464 | issue = 7289 | pages = 757–62 | date = Apr 2010 | pmid = 20360741 | pmc = 3187626 | doi = 10.1038/nature08819 }}</ref>

It is also predicted computationally that the miR-138 gene exists in the [[genome]] of other animals including [[horse]] (''Equus caballus''),<ref name="PMID19406225">{{cite journal | vauthors = Zhou M, Wang Q, Sun J, Li X, Xu L, Yang H, Shi H, Ning S, Chen L, Li Y, He T, Zheng Y | title = In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach | journal = Genomics | volume = 94 | issue = 2 | pages = 125–31 | date = Aug 2009 | pmid = 19406225 | doi = 10.1016/j.ygeno.2009.04.006 }}</ref> [[rhesus macaque]] (''Macaca mulatta''),<ref name=PMID18186931>{{cite journal | vauthors = Yue J, Sheng Y, Orwig KE | title = Identification of novel homologous microRNA genes in the rhesus macaque genome | journal = BMC Genomics | volume = 9 | issue = 1 | pages = 8 | date = 10 January 2008 | pmid = 18186931 | pmc = 2254598 | doi = 10.1186/1471-2164-9-8 }}</ref> [[takifugu rubripes]] (''Fugu rubripes''), [[Bornean orangutan]] (''Pongo pygmaeus''),<ref name=PMID20214803>{{cite journal | vauthors = Brameier M | title = Genome-wide comparative analysis of microRNAs in three non-human primates | journal = BMC Research Notes | volume = 3 | issue = 1 | pages = 64 | date = 9 March 2010 | pmid = 20214803 | doi = 10.1186/1756-0500-3-64 | pmc=2850348}}</ref> [[common chimpanzee]] (''Pan troglodytes''),<ref name=PMID18760970>{{cite journal | vauthors = Baev V, Daskalova E, Minkov I | title = Computational identification of novel microRNA homologs in the chimpanzee genome | journal = Computational Biology and Chemistry | volume = 33 | issue = 1 | pages = 62–70 | date = Feb 2009 | pmid = 18760970 | doi = 10.1016/j.compbiolchem.2008.07.024 }}</ref> ''[[Tetraodon nigroviridis]]'' and [[western clawed frog]] (''Xenopus tropicalis'').

== Genomic location ==
In human genome, there are two miR-138 associated genes and they are not located in any cluster. More precisely, the miR-138-1 gene is in region 5 at 3p21.3<ref name=PMID14973191>{{cite journal | vauthors = Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM | title = Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 9 | pages = 2999–3004 | date = Mar 2004 | pmid = 14973191 | pmc = 365734 | doi = 10.1073/pnas.0307323101 }}</ref> and miR-138-2 is located on [[chromosome 16]] (16q13).<ref name=PMID19540661>{{cite journal | vauthors = Liu X, Jiang L, Wang A, Yu J, Shi F, Zhou X | title = MicroRNA-138 suppresses invasion and promotes apoptosis in head and neck squamous cell carcinoma cell lines | journal = Cancer Letters | volume = 286 | issue = 2 | pages = 217–22 | date = Dec 2009 | pmid = 19540661 | doi = 10.1016/j.canlet.2009.05.030 | pmc=2783372}}</ref>

== Pattern of expression ==
In adult mice, miR-138 is only expressed in [[brain]] tissue. Its expression is not uniform throughout the brain but restricted to distinct neuronal populations. On the contrary, its precursor, pre-miR-138-2, is ubiquitously expressed throughout all tissues, which suggests that the expression of miRNAs can be regulated at the post-transcription level.<ref name="PMID16738409" />

In the zebrafish, miR-138 is expressed in specific domains in the [[heart]] and is required to establish appropriate chamber-specific [[gene expression]] patterns.<ref name=PMID19004786>{{cite journal | vauthors = Morton SU, Scherz PJ, Cordes KR, Ivey KN, Stainier DY, Srivastava D | title = microRNA-138 modulates cardiac patterning during embryonic development | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 46 | pages = 17830–5 | date = Nov 2008 | pmid = 19004786 | pmc = 2582580 | doi = 10.1073/pnas.0804673105 }}</ref>

==Targets and function==
Since the identification of miR-138, a number of targets have been found and some of them have been verified experimentally. It has been proven that miR-138 is involved in different pathways. Furthermore, it is in relation with various types of [[cancer]].

;HIF-1a: [[Hypoxia-inducible factor]]-1alpha (HIF-1a), one of the key regulators in cancer cells, has been shown to be one target of miR-138.<ref name="PMID21875287">{{cite journal | vauthors = Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J, Hong B | title = MiR-138 suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in clear cell renal cell carcinoma 786-O cells | journal = Asian Pacific Journal of Cancer Prevention | volume = 12 | issue = 5 | pages = 1307–11 | year = 2011 | pmid = 21875287 }}</ref>
;VIM, ZEB2, EZH2 and head and neck cancers: Downregulation of miR-138 has been reported in several types of cancers, including [[head and neck cancers|HNSCC]](head and neck squamous cell carcinoma). It is suggested that miR-138 is a multi-functional molecular regulator and plays major roles in EMT ([[epithelial-mesenchymal transition]]) and in HNSCC progression. A number of miR-138 target genes have been identified to be associated with EMT, including VIM ([[vimentin]]), [[ZEB2]] (zinc finger E-box-binding homeobox 2) and [[EZH2]] (enhancer of zeste homologue 2).<ref name="PMID21770894">{{cite journal | vauthors = Liu X, Wang C, Chen Z, Jin Y, Wang Y, Kolokythas A, Dai Y, Zhou X | title = MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines | journal = The Biochemical Journal | volume = 440 | issue = 1 | pages = 23–31 | date = Nov 2011 | pmid = 21770894 | pmc = 3331719 | doi = 10.1042/BJ20111006 }}</ref>
;CCND1 and nasopharyngeal carcinoma:miR-138 is commonly underexpressed in [[nasopharyngeal carcinoma]] (NPC) specimens and NPC cell lines. [[Cyclin D1]] (CCND1), which is widely upregulated in NPC tumors, is found as a direct target of miR-138. Therefore, miR-138 might be a tumor suppressor in NPC, which is exerted partially by inhibiting CCND1 expression.<ref name=PMID22739938>{{cite journal | vauthors = Liu X, Lv XB, Wang XP, Sang Y, Xu S, Hu K, Wu M, Liang Y, Liu P, Tang J, Lu WH, Feng QS, Chen LZ, Qian CN, Bei JX, Kang T, Zeng YX | title = MiR-138 suppressed nasopharyngeal carcinoma growth and tumorigenesis by targeting the CCND1 oncogene | journal = Cell Cycle | volume = 11 | issue = 13 | pages = 2495–506 | date = Jul 2012 | pmid = 22739938 | doi = 10.4161/cc.20898 }}</ref>
;BCR-ABL and CCND3: [[BCR (gene)|BCR]] (breakpoint cluster region)-[[ABL (gene)|ABL]] (c-abl oncogene 1, non-receptor tyrosine kinase)/[[GATA1]]/miR-138 mini circuitry contributes to the leukemogenesis of [[chronic myeloid leukemia]] (CML). ABL and BCR-ABL are the target genes of miR-138, which binds to the [[coding region]] instead of [[three prime untranslated region]] (3'UTR). miR-138 can negatively regulate another gene [[Cyclin D3|CCND3]] via binding to its 3'-UTR. The expression of miR-138 is activated by GATA1, which in turn is repressed by BCR-ABL. Therefore, miR-138, by virtue of a BCR-ABL/GATA1/miR-138 circuitry, is a tumor suppressor miRNA implicated in the pathogenesis of CML and its clinical response to [[imatinib]].<ref name=PMID23208504>{{cite journal | vauthors = Xu C, Fu H, Gao L, Wang L, Wang W, Li J, Li Y, Dou L, Gao X, Luo X, Jing Y, Chim CS, Zheng X, Yu L | title = BCR-ABL/GATA1/miR-138 mini circuitry contributes to the leukemogenesis of chronic myeloid leukemia | journal = Oncogene | volume = 33 | issue = 1 | pages = 44–54 | date = Jan 2014 | pmid = 23208504 | doi = 10.1038/onc.2012.557 }}</ref>
;H2AX and DNA damage repair: mir-138 is linked with DNA damage repair. It can directly target the [[histone]] [[H2AFX|H2AX]] 3'UTR, reduce histone H2AX expression and induce chromosomal instability after DNA damage.<ref name="PMID21693595">{{cite journal | vauthors = Wang Y, Huang JW, Li M, Cavenee WK, Mitchell PS, Zhou X, Tewari M, Furnari FB, Taniguchi T | title = MicroRNA-138 modulates DNA damage response by repressing histone H2AX expression | journal = Molecular Cancer Research | volume = 9 | issue = 8 | pages = 1100–11 | date = Aug 2011 | pmid = 21693595 | pmc = 3157593 | doi = 10.1158/1541-7786.MCR-11-0007 }}</ref>
;ALDH1A2 and CSPG2: In zebrafish, the mature form of miR-138 regulates gene expression influencing cardiac development. miR-138 helps establish discrete domains of gene expression during cardiac morphogenesis by targeting multiple members of a common pathway. It has been experimentally verified that miR-138 can negatively regulate ''[[ALDH1A2|aldh1a2]]'', encoding [[retinoic acid]] (RA) dehydrogenase (Raldh2), by targeting the binding site in the 3'UTR of its mRNA. Another putative target of miR-138 is ''[[Versican|cspg2]]''.<ref name="PMID19004786" />
;Regulation of sleep: In rats, miR-138, [[let-7 microRNA precursor|let-7]]b, and miR-125a are expressed at different times and in different structures in the brain and likely play a role in the regulation of sleep.<ref name=PMID23104698>{{cite journal | vauthors = Davis CJ, Clinton JM, Krueger JM | title = MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats | journal = Journal of Applied Physiology | volume = 113 | issue = 11 | pages = 1756–62 | date = Dec 2012 | pmid = 23104698 | doi = 10.1152/japplphysiol.00940.2012 | pmc=3544506}}</ref>
;Brain cancer: miR-138 has been found to be significantly linked with the formation and growth of [[Glioma]]s, from [[Cancer Stem Cell|Cancerous Stem Cells]] (CSC). In vitro inhibition of miR-138 prevents tumour sphere formation. Furthermore, its high expression in Glioma makes it a potential biomarker for CSC.<ref name=PMID22921398>{{cite journal | vauthors = Chan XH, Nama S, Gopal F, Rizk P, Ramasamy S, Sundaram G, Ow GS, Ivshina AV, Tanavde V, Haybaeck J, Kuznetsov V, Sampath P | title = Targeting glioma stem cells by functional inhibition of a prosurvival oncomiR-138 in malignant gliomas | journal = Cell Reports | volume = 2 | issue = 3 | pages = 591–602 | date = Sep 2012 | pmid = 22921398 | doi = 10.1016/j.celrep.2012.07.012 }}</ref>
;Rhoc, ROCK2 and Tongue cancer: Tumour metastasis concerning the Tongue Squamous Cell Carcinoma (TSCC) can be regulated via the expression of 2 key genes in Rho GTPase signaling pathway : [[RhoC]] and ROCK2 ([[Rho-associated protein kinase]] 2). Thus, by targeting the 3' untranslated region of those genes, mir-138 is able to reduce their expression and by this mean, to destroy TSCC ability migrate and invade.<ref name=PMID20232393>{{cite journal | vauthors = Jiang L, Liu X, Kolokythas A, Yu J, Wang A, Heidbreder CE, Shi F, Zhou X | title = Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma | journal = International Journal of Cancer | volume = 127 | issue = 3 | pages = 505–12 | date = Aug 2010 | pmid = 20232393 | doi = 10.1002/ijc.25320 | pmc=2885137}}</ref>

== References ==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, Zerbib M, Lidereau R, Debre B, Amsellem-Ouazana D, Bieche I | title = microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer | journal = International Journal of Cancer | volume = 132 | issue = 11 | pages = 2479–91 | date = Jun 2013 | pmid = 23169479 | doi = 10.1002/ijc.27949 }}
* {{cite journal | vauthors = Ye D, Wang G, Liu Y, Huang W, Wu M, Zhu S, Jia W, Deng AM, Liu H, Kang J | title = MiR-138 promotes induced pluripotent stem cell generation through the regulation of the p53 signaling | journal = Stem Cells | volume = 30 | issue = 8 | pages = 1645–54 | date = Aug 2012 | pmid = 22696098 | doi = 10.1002/stem.1149 }}
* {{cite journal | vauthors = Jin Y, Wang C, Liu X, Mu W, Chen Z, Yu D, Wang A, Dai Y, Zhou X | title = Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma | journal = The Journal of Biological Chemistry | volume = 286 | issue = 46 | pages = 40104–9 | date = Nov 2011 | pmid = 21969367 | doi = 10.1074/jbc.c111.296707 | pmc=3220531}}
* {{cite journal | vauthors = Eskildsen T, Taipaleenmäki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, Bak M, Kauppinen S, Kassem M | title = MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 15 | pages = 6139–44 | date = Apr 2011 | pmid = 21444814 | doi = 10.1073/pnas.1016758108 | pmc=3076836}}
* {{cite journal | vauthors = Muiños-Gimeno M, Espinosa-Parrilla Y, Guidi M, Kagerbauer B, Sipilä T, Maron E, Pettai K, Kananen L, Navinés R, Martín-Santos R, Gratacòs M, Metspalu A, Hovatta I, Estivill X | title = Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways | journal = Biological Psychiatry | volume = 69 | issue = 6 | pages = 526–33 | date = Mar 2011 | pmid = 21168126 | doi = 10.1016/j.biopsych.2010.10.010 }}
* {{cite journal | vauthors = Kisliouk T, Yosefi S, Meiri N | title = MiR-138 inhibits EZH2 methyltransferase expression and methylation of histone H3 at lysine 27, and affects thermotolerance acquisition | journal = The European Journal of Neuroscience | volume = 33 | issue = 2 | pages = 224–35 | date = Jan 2011 | pmid = 21070394 | doi = 10.1111/j.1460-9568.2010.07493.x }}
* {{cite journal | vauthors = Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC | title = MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1 | journal = Stem Cells and Development | volume = 20 | issue = 2 | pages = 259–67 | date = Feb 2011 | pmid = 20486779 | doi = 10.1089/scd.2010.0072 }}
{{refend}}

== External links ==
{{miRNA precursor families}}
[[:Category:MicroRNA]]