View source for Mir-19 microRNA precursor family

{{Infobox rfam
| Name = mir-19 microRNA precursor family
| image = RF00245.jpg
| width =
| caption = Predicted [[secondary structure]] and [[sequence conservation]] of mir-19
| Symbol = mir-19
| AltSymbols =
| Rfam = RF00245
| miRBase = MI0000073
| miRBase_family = MIPF0000011
| RNA_type = [[Gene]]; [[MicroRNA|miRNA]]
| Tax_domain = [[Eukaryota]]
| GO = {{GO|0035195}} {{GO|0035068}}
| SO = {{SO|0001244}}
| CAS_number =
| EntrezGene =
| HGNCid =
| OMIM =
| PDB =
| RefSeq =
| Chromosome =
| Arm =
| Band =
| LocusSupplementaryData =
}}

There are 89 known sequences today in the microRNA 19 (miR-19) family but it will change quickly. They are found in a large number of [[vertebrate]] species. The miR-19 microRNA precursor is a small [[non-coding RNA]] molecule that regulates [[gene expression]]. Within the human and mouse [[genome]] there are three copies of this [[microRNA]] that are processed from multiple predicted precursor [[Stem-loop|hairpins]]:<ref name=art1>{{cite journal | last = Lagos-Quintana | first = M |author2=Rauhut R |author3=Lendeckel W |author4=Tuschl T  | year = 2001 | title = Identification of novel genes coding for small expressed RNAs | journal = Science | volume = 294 | pages = 853–858 | pmid = 11679670 | doi = 10.1126/science.1064921 | issue = 5543| bibcode = 2001Sci...294..853L | hdl = 11858/00-001M-0000-0012-F65F-2 }}</ref><ref>{{cite journal | last = Mourelatos | first = Z |author2=Dostie J |author3=Paushkin S |author4=Sharma A |author5=Charroux B |author6=Abel L |author7=Rappsilber J |author8=Mann M |author9=Dreyfuss G   | year = 2002 | title=miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs | journal = Genes Dev | volume = 16 | pages = 720&ndash;728 | pmid = 11914277 | doi = 10.1101/gad.974702 | issue = 6 | pmc = 155365}}</ref><ref name=pmid12919684>{{cite journal | last = Houbaviy | first = HB |author2=Murray MF |author3=Sharp PA  | year = 2003 | title = Embryonic stem cell-specific MicroRNAs | journal = Dev Cell | volume = 5 | pages = 351&ndash;358 | pmid = 12919684 | doi = 10.1016/S1534-5807(03)00227-2 | issue = 2}}</ref>

* mouse:
: * miR-19a on chromosome 14 ([https://archive.is/20121223041415/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_entry.pl?acc=MI0000688 MI0000688])
: * miR-19b-1 on chromosome 14 ([http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000718 MI0000718])
: * miR-19b-2 on chromosome X ([https://archive.is/20121223072658/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_entry.pl?acc=MI0000546 MI0000546])
* human:<ref name=art1 />
: * miR-19a on chromosome 13 ([http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000073 MI0000073])
: * miR-19b-1 on chromosome 13 ([https://archive.is/20121223171808/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_entry.pl?acc=MI0000074 MI0000074])
: * miR-19b-2 on chromosome X ([http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000075 MI000075]).

MiR-19 has now been predicted or experimentally confirmed  ([http://www.mirbase.org/cgi-bin/mirna_summary.pl?fam=MIPF0000011 MIPF0000011]). In this case the mature sequence is excised from the 3' arm of the [[stem-loop|hairpin]] precursor.

== Origins ==
MicroRNA are ubiquitous in higher [[eukaryotes]], and show varying patterns of expression in specific cell types.<ref name=mamalian>{{cite journal | last = Landgraf | first = P |author2=M Rusu |author3=R Sheridan |author4=A Sewer  | year = 2007 | title = A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing | journal = Cell | volume = 129 | pages = 1401–1414 | pmid = 17604727 | issue = 7| doi=10.1016/j.cell.2007.04.040 | pmc=2681231}}</ref> MiR-19 has been identified in a diverse range of [[vertebrate]] animals including [[green anole]] (''Anolis carolinensis''),<ref>{{cite journal |author1=Lyson TR |author2=Sperling EA |author3=Heimberg AM and al. |title=MicroRNAs support a turtle + lizard clade |journal=Biol Lett |volume = 8 | pages = 104–7 | pmid = 21775315 | doi = 10.1098/rsbl.2011.0477 | issue =1 |year=2012 | pmc=3259949}}</ref> [[primates]] (gorilla, human, ...),<ref>{{cite journal |author=Berezikov E, Guryev V, van de Belt J and al. |title=Phylogenetic shadowing and computational identification of human microRNA genes |journal=Cell |volume=120 | pages=21–4 | pmid =15652478 | issue =1 |year=2005 | doi=10.1016/j.cell.2004.12.031}}</ref><ref>{{cite journal |author1=Lui WO |author2=Pourmand N |author3=Patterson BK and al. |title=Patterns of known and novel small RNAs in human cervical cancer |journal=Cancer Res | year=2007  |volume=67 | issue=13 | pages=6031–43 | pmid =17616659 | doi= 10.1158/0008-5472.CAN-06-0561}}</ref> [[cattle]] (''Bos taurus''),<ref>{{cite journal |vauthors=Gu Z, Eleswarapu S, Jiang H |title=Identification and characterization of microRNAs from the bovine adipose tissue and mammary gland |journal=FEBS Lett |volume=581 | pages=981–8 | pmid=17306260 | issue=5 |year=2007 | doi=10.1016/j.febslet.2007.01.081}}</ref> [[dog]] (''Canis familiaris''),<ref>{{cite journal |author1=Friedländer MR |author2=Chen W |author3=Adamidi C and al. |title=Discovering microRNAs from deep sequencing data using miRDeep |journal=Nat Biotechnol |year=2008 |volume=26 | issue=4 | pages = 407–15 | pmid=18392026 | doi = 10.1038/nbt1394}}</ref> [[Chinese hamster]] (''Cricetulus griseus''),<ref>{{cite journal |author1=Hackl M |author2=Jakobi T |author3=Blom J and al. |title=Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering |journal=J Biotechnol |year=2011 |volume=153 | issue=1–2 | pages = 62–75 | pmid=21392545 | doi = 10.1016/j.jbiotec.2011.02.011 | pmc=3119918}}</ref> [[zebrafish]] (''Danio rerio''),<ref name="pmid15937218">{{cite journal |author1=Chen PY |author2=Manninga H |author3=Slanchev K and al. |title=The developmental miRNA profiles of zebrafish as determined by small RNA cloning | journal=Genes Dev |year=2005 |volume=19 | issue=11 | pages = 1288–93 | pmid=15937218 | doi =  10.1101/gad.1310605 | pmc=1142552}}</ref> [[horse]] (''Equus caballus''),<ref>{{cite journal |author1=Zhou M |author2=Wang Q |author3=Sun J and al. |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 |year=2009 |volume=94 | issue=2 | pages=125–31 | pmid=19406225 | doi=10.1016/j.ygeno.2009.04.006}}</ref> ''[[Takifugu rubripes]]'',<ref name="pmid15937218" />''[[Tetraodon nigroviridis]]'',<ref name="pmid15937218" /> [[chicken]] (''Gallus gallus''),<ref>{{cite journal |author=International Chicken Genome Sequencing Consortium |title=Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution | journal=Nature |year=2004 |volume=432 | issue=7018 | pages=695–716 | pmid=15592404 | doi=10.1038/nature03154|bibcode=2004Natur.432..695C |url=https://escholarship.org/content/qt44v0c3r5/qt44v0c3r5.pdf?t=or4mqz }}</ref><ref>{{cite journal |author1=Yao Y |author2=Zhao Y |author3=Xu H and al. |title=MicroRNA profile of Marek's disease virus-transformed T-cell line MSB-1: predominance of virus-encoded microRNAs | journal=J Virol |year=2008 |volume=82 | issue=8 | pages=4007–15 | pmid=18256158 | doi=10.1128/JVI.02659-07 | pmc=2293013}}</ref> [[gray short-tailed opossum]] (''Monodelphis domestica''),<ref>{{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=J Hered |year=2008 |volume=99 | issue=1 | pages=66–72 | pmid=17965199 | doi=10.1093/jhered/esm085}}</ref> [[platypus]] (''Ornithorhynchus anatinus''),<ref>{{cite journal |author1=Murchison EP |author2=Kheradpour P |author3=Sachidanandam R and al. |title=Conservation of small RNA pathways in platypus | journal=Genome Res |year=2008 |volume=18 | issue=6 | pages=995–1004 | pmid=18463306 | doi=10.1101/gr.073056.107 | pmc=2413167}}</ref> [[Oryzias latipes|Japanese medaka]] (''Oryzias latipes''),<ref>{{cite journal |author1=Li SC |author2=Chan WC |author3=Ho MR and al. |title=Discovery and characterization of medaka miRNA genes by next generation sequencing platform | journal=BMC Genomics |year=2010 |volume= 11 Suppl 4| issue= | pages= S8| pmid=21143817 | doi=10.1186/1471-2164-11-S4-S8 | pmc=3005926}}</ref> [[African clawed frog]] (''Xenopus laevis''),<ref>{{cite journal |author1=Watanabe T |author2=Takeda A |author3=Mise K and al. |title=Stage-specific expression of microRNAs during Xenopus development | journal=FEBS Lett |year=2005 |volume=579 | issue=2 | pages=318–24 | pmid=15642338 | doi=10.1016/j.febslet.2004.11.067}}</ref> [[Tasmanian devil]] (''Sarcophilus harrisii''),<ref>{{cite journal |author1=Murchison EP |author2=Tovar C |author3=Hsu A and al. |title=The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer | journal=Science |year=2010 |volume=327 | issue=5961 | pages=84–7 | pmid=20044575 | doi=10.1126/science.1180616 | pmc=2982769|bibcode=2010Sci...327...84M }}</ref> [[pig]] (''Sus scrofa'')<ref>{{cite journal |author1=Wernersson R |author2=Schierup MH |author3=Jørgensen FG and al. |title=Pigs in sequence space: a 0.66X coverage pig genome survey based on shotgun sequencing | journal=BMC Genomics |year=2005 |volume= 6| issue= | pages=6:70 | pmid=15885146 | doi=10.1186/1471-2164-6-70 | pmc=1142312}}</ref> and [[zebra finch]] (''Taeniopygia guttata'').<ref>{{cite journal |author1=Warren WC |author2=Clayton DF |author3=Ellegren H and al. |title=The genome of a songbird | journal=Nature |year=2010 |volume=464 | issue=7289 | pages=757–62 | pmid=20360741 | doi=10.1038/nature08819 | pmc=3187626|bibcode=2010Natur.464..757W }}</ref> In some of these species the presence of miR-19 microRNAs have been directly measured, in other species genes have been identified with sequences that are predicted to encode miR-19.<ref name=art1 />

== Expression ==

MiR-17-92 [[gene cluster|cluster]] was identified to encode 6 single mature miRNA ([[miR-17]], [https://www.ncbi.nlm.nih.gov/pubmed/20724452|miR-18], miR-19, [[Mir-20 microRNA precursor family|miR-20]], [[Mir-92 microRNA precursor family|miR-92]], [[Mir-106 microRNA precursor family|miR-106]]) containing the first oncogenic miRNA.

MicroRNA from miR-19 family can be expressed from:
: * [[T-lymphoblastic leukemia/lymphoma|T-cell acute lymphoblastic leukemia]] <ref name="1137–1139">{{cite journal |author1=Huashan Ye |author2=Xiaowen Liu |author3=Meng Lv |author4=Yuliang Wu |author5=Shuzhen Kuang |author6=Jing Gong |author7=Ping Yuan |author8=Zhaodong Zhong |author9=Qiubai Li |author10=Haibo Jia |author11=Jun Sun |author12=Zhichao Chen |author13=An-Yuan Guo |title=MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia |journal=Nucleic Acids Research |volume=40 |issue=12 |pages=5201–14 |year=2012|doi=10.1093/nar/gks175 |pmid=22362744 |pmc=3384304 }}</ref>
: * [[B-cell CLL/lymphoma|B-cell lymphomas]] <ref name="pmid20008931">{{cite journal |author1=Ping Mu |author2=Yoon-Chi Han |author3=Doron Betel |author4=Evelyn Yao |author5=Massimo Squatrito |author6=Paul Ogrodowski |author7=Elisa de Stanchina |author8=Aleco D'Andrea |author9=Chris Sander |author10=Andrea Ventura |title=Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas |journal=Genes Dev |volume=23 | issue=24 | pages=2806–11 |year=2009 |pmid=20008931 |pmc=2800095 |doi=10.1101/gad.1872909 |url=}}</ref>
: * [[Cell lines]] <ref name="1137–1139" />
: * [[Cerebellum]] <ref name="pmid18758459">{{cite journal |vauthors=Lee Y, Samaco RC, Gatchel JR, Thaller C, Orr HT, Zoghbi HY |title=miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis |journal=Nat. Neurosci. |volume=11 |issue=10 |pages=1137–9 |date=October 2008 |pmid=18758459 |pmc=2574629 |doi=10.1038/nn.2183 |url=}}</ref><ref name="pmid21200023">{{cite journal |author1=Alexander Baraniskin |author2=Jan Kuhnhenn |author3=Uwe Schlegel |author4=Andrew Chan |author5=Martina Deckert |author6=Ralf Gold |author7=Abdelouahid Maghnouj |author8=Hannah Zöllner |author9=Anke Reinacher-Schick |author10=Wolff Schmiegel |author11=Stephan A. Hahn |author12=Roland Schroers |title=Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system |journal=Blood |volume=117 | issue= 11| pages=3140–3146 |year=2011 |pmid=21200023 |pmc= |doi=10.1182/blood-2010-09-308684 |url=}}</ref>
: * [[Purkinje cells]] <ref name="pmid18758459" />
: * [[HeLa cells]] <ref name="pmc3439911">{{cite journal |author1=Michael P. Gantier |author2=H. James Stunden |author3=Claire E. McCoy |author4=Mark A. Behlke |author5=Die Wang |author6=Maria Kaparakis-Liaskos |author7=Soroush T. Sarvestani |author8=Yuan H. Yang |author9=Dakang Xu |author10=Sinéad C. Corr |author11=Eric F. Morand |author12=Bryan R. G. Williams |title=A miR-19 regulon that controls NF-iB signaling |journal=Nucleic Acids Research |volume=40 | issue=16 | pages=8048–8058 |year=2012 |pmid= 22684508|pmc=3439911 |doi=10.1093/nar/gks521 |url=}}</ref>

Finally they have tissues-specific miRNA expression. These microRNA are considered as [[oncogene]]s which improve [[Cell growth|proliferation]], [[Enzyme inhibitor|inhibits]] [[apoptosis]] and induce [[tumor]] [[angiogenesis]].<ref name="pmid21059650">{{cite journal |author1=Xiaoxi Zhang |author2=Haijun Yu |author3=Jessica R. Lou |author4=Jie Zheng |author5=Hua Zhu |author6=Narcis-Ioan Popescu |author7=Florea Lupu |author8=Stuart E. Lind |author9=Wei-Qun Ding  |last-author-amp=yes |title=MicroRNA-19 (miR-19) Regulates Tissue Factor Expression in Breast Cancer Cells |journal=The Journal of Biological Chemistry |volume=286 | issue= 2| pages=1429–1435 |year=2011 |pmid=21059650 |pmc=3020751 |doi=10.1074/jbc.M110.146530 |url=}}</ref>
<br/>
These miRNA are context-specific and they have different roles depending on where they are.

== miR-19a/b roles ==

=== Acute lymphoblastic leukemia ===
[[Ectopic expression]] of miR-19 represses [[Cylindromatosis|CYLD]] expression, while miR-19 inhibitor treatment induces CYLD protein expression and decreases [[NF-kB]] expression in the [[Upstream and downstream (transduction)|downstream signaling pathway]].
Thus, miR-19, CYLD and NF-kB form a regulatory [[feed forward (control)|feedforward]] loop, which provides new clues for sustained activation of NF-kB in [[T-cell]] acute [[lymphoblast]]ic [[leukemia]].<ref name="1137–1139" /><br/>
MiR-19 is sufficient to induce T-cell lymphoblastic leukemia activating [[Notch-1|Notch1]] and accelerate the [[Acute lymphoblastic leukemia|disease]]. Its targets are:
: * [[BCL2L11|Bim (Bcl2L11)]] gene
: * [[Protein kinase, AMP-activated, alpha 1|AMP-activated kinase (Prkaa1)]] gene
: * [[E2F1]] gene
: * the tumour suppressor phosphatases [[PTEN (gene)|PTEN]]
: * [[PPP2R5E|PP2A (Ppp2r5e)]] gene
: * [[Dock5]] protein
MiR-19b coordinates a [[PI3K/AKT/mTOR pathway|PI3K pathway]] acting on cell survival in lymphocytes contributing to leukaemogenesis.<ref name="pmid20190740">{{cite journal |author=Konstantinos J. Mavrakis1, Andrew L. Wolfe, Elisa Oricchio1, Teresa Palomero and al. |title=Genome-wide RNAi screen identifies miR-19 targets in Notchinduced acute T-cell leukaemia (T-ALL) |journal=Nat Cell Biol |volume=12 | issue=4 | pages=372–379 |year=2011 |pmid=20190740 |pmc=2989719 |doi=10.1038/ncb2037 |url=}}</ref><ref name="pmid20505335">{{cite journal |author1=Konstantinos J. Mavrakis  |author2=Hans-Guido Wendel  |lastauthoramp=yes |title=TargetScreen: an unbiased approach to identify functionally important microRNA targets |journal=Cell Cycle |volume=9 | issue=11 | pages=2080–4 |year=2010 |pmid=20505335|pmc= |doi= 10.4161/cc.9.11.11807|url=}}</ref><ref name="pmid17575136">{{cite journal |author1=Séverine Landais |author2=Sébastien Landry |author3=Philippe Legault and al. |title=Oncogenic Potential of the miR-106-363 Cluster and Its Implication in Human T-Cell Leukemia |journal=Cancer Res |volume=67 | issue=12 | pages=5699–707 |year=2007 |pmid=17575136 |pmc= |doi=10.1158/0008-5472.CAN-06-4478 |url=}}</ref>

This pathway is activated through PTEN loss and can contribute to reduce sensitivity to [[chemotherapy]] and (in [[Adult T-cell leukemia/lymphoma|T-ALL]]) may impact the effectiveness of therapeutic [[Gamma secretase|gamma-secretase]] inhibitors.

=== Primary central nervous system lymphoma ===
Baraniskin and al. study show that [[mIRN21|miR-21]], miR-19, and [[mir-92 microRNA precursor family|miR-92a]] levels in [[cerebrospinal fluid]] (CSF) seems to be good [[biomarker]]s to diagnose a [[Primary central nervous system lymphoma]] (PCNSL). They also demonstrate that miRNAs in [[Cytoplasm|plasma]] are in a resistant form to intrinsic [[Ribonuclease|RNase]] activity, and there is a low RNase activity in the CSF.<ref name="pmid21200023" />

=== B-cell lymphomas ===
MiR-19 has been identified as a key responsible for the oncogenic activity, reducing the tumor suppressor gene [[PTEN (gene)|PTEN]] expression and activating [[PI3K/AKT/mTOR pathway|AKT/mTOR pathway]]. This cluster might be important regulator on cancer and aging.<ref name="pmid20437201">{{cite journal |author1=Johannes Grillari |author2=Matthias Hackl |author3=Regina Grillari-Voglauer |title=miR-17–92 cluster: ups and downs in cancer and aging |journal=Biogerontology |volume=11 | issue= 4| pages=501–506 |year=2010 |pmid=20437201 |pmc=2899009 |doi=10.1007/s10522-010-9272-9 |url=}}</ref><ref name="pmid20008935">{{cite journal |author=Virginie Olive, Margaux J. Bennett, James C. Walker and al. |title=miR-19 is a key oncogenic component of mir-17-92 |journal=Genes Dev |volume=23 | issue=24 | pages=2839–49 |year=2009 |pmid=20008935 |pmc=2800084 |doi=10.1101/gad.1861409 |url=}}</ref><br/>
Mu and al. demonstrated that the expression of endogenous miR-17-92 is required to suppress [[apoptosis]] in [[Myc]]-driven [[B-cell CLL/lymphoma|B-cell]] [[lymphoma]]s. More specifically, miR-19a and miR-19b are required and sufficient to recapitulate the oncogenic properties of the entire cluster.<ref name="pmid20008931" /><ref name="pmid18728182" />
Using prediction algorithms, they found miR-19 targets to the pro-survival functions:
: * [[PTEN (gene)|PTEN]] tumor suppressor gene
: * PTEN mRNA
: * [[SBF2|Sbf2]] gene
: * Bcl7a gene
: * Rnf44 gene

=== Keratinocytes ===
In the cell response to [[Stress (biology)|stress]], the most important is the post-transcriptional control of the important gene expression to cell survival and [[apoptosis]]. MiR-19 regulates the [[RHOB|Ras homolog B (RhoB)]] expression in [[keratinocyte]]s after [[ultraviolet]] (UV) radiation exposition. This phenomenon needs the binding of [[ELAVL1|human antigen R (HuR)]] to the rhoB mRNA [[Three prime untranslated region|3'-untranslated region]].
In this case, HuR acts positively on miRNA action. The interaction between HuR and miR-19 with rhoB is lost under UV treatment. Here, miR-19, linked to RhoB, acts like a protector against keratinocyte apoptosis. A 52-[[nucleotide]]-long sequence of the rhoB 3'-UTR spanning bases 818–870, containing the miR-19 and the HuR binding site was sufficient for UV regulation. This event is UV dependent!<ref name="pmid21527938">{{cite journal |author1=V Glorian |author2=G Maillot |author3=S Polès and al. |title=HuR-dependent loading of miRNA RISC to the mRNA encoding the Ras-related small GTPase RhoB controls its translation during UV-induced apoptosis |journal=Cell Death and Differentiation |volume=18 | issue= 11| pages=1692–1701 |year=2011 |pmid=21527938 |pmc=3190107 |doi=10.1038/cdd.2011.35 |url=}}</ref>

=== Multiple myeloma ===
One study on [[multiple myeloma]] patients permitted to identified a selective up-regulation of [[Mir-32 microRNA precursor family|miR-32]] and the miR-17-92 cluster. MiR-19a and miR-19b were shown to down regulate [[Suppressor of cytokine signaling 1|SOCS-1]] expression (a specific gene that inhibits [[Interleukin 6|IL-6]] growth signaling). Therefore, miR-17-92 with [[mIRN21|miR-21]], inhibits apoptosis and promotes cell survival.<ref name="pmid18728182">{{cite journal |author1=Flavia Pichiorri |author2=Sung-Suk Suh |author3=Marco Ladetto and al. |title=MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=105 | issue=35 | pages=12885–90 |year=2008 |pmid=18728182 |pmc=2529070 |doi=10.1073/pnas.0806202105 |url=|bibcode=2008PNAS..10512885P }}</ref>

=== Retinoblastoma ===
In this case, miR-17-92 cluster promotes [[retinoblastoma]] due to loss of [[Retinoblastoma protein|Rb family members]]. The mouse retinal development need miR-17-92 over-expression with Rb and p107 deletion, but it occurred frequent emergence of retinoblastoma and [[metastasis]] to the brain.<br/>
Here, the cluster oncogenic function is not mediated by a miR-19/PTEN axis toward apoptosis suppression like in [[lymphoma]] or in [[leukemia]] models. MiR-17-92 increase the proliferative capacity of Rb/p107-deficient in [[Retina|retinal cells]].<br/>
Moreover, the Rb family members deletion led to compensatory up-regulation of the [[p21|cyclin-dependent kinase inhibitor p21Cip1]].<br/>
Finally, the cluster over-expression counteracted p21Cip1 up-regulation, promotes proliferation and drove retinoblastoma formation.<ref name="pmid21816922">{{cite journal |author1=Karina Conkrite |author2=Maggie Sundby |author3=Shizuo Mukai and al. |title=miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma |journal=Genes & Development |volume=25 | issue=16 | pages=1734–45 |year=2011 |pmid=21816922 |pmc=3165937 |doi=10.1101/gad.17027411 |url=}}</ref>

=== Role in normal development of heart, lungs and immune system ===
Scientists observed that the loss of function of the miR-17-92 cluster is induced in smaller [[embryo]]s and postnatal deaths.<ref name="pmid18423194" /> The specific role of this cluster in heart and lung [[Developmental biology|development]] remains unclear, but the observations described above show that these miRNAs are normally highly expressed in embryonic lung and decrease with maturity. Moreover, [[Transgenesis|transgenic]] expression of these miRNAs specifically in lung epithelium results in severe developmental defects with enhanced proliferation and
inhibition of [[Cellular differentiation|differentiation]] of [[Epithelium|epithelial cells]].<br/>
Furthermore, mouse hematopoiesis occurring in the absence of miR-17-92 leads to an isolated defect in B cell development.<ref name="pmid18423194">{{cite journal |author=Joshua T. Mendell |title=miRiad roles for the miR-17-92 cluster in development and disease |journal=Cell |volume=133 | issue=2 | pages=217–22 |year=2008 |pmid=18423194 |pmc=2732113 |doi=10.1016/j.cell.2008.04.001 |url=}}</ref>

=== Role in the endothelial differentiation of stem cells ===
The miR-17-92 cluster containing miR-19 miRNA family is also involved into control [[Endothelium|endothelial cell functions]] and neo-vascularization. MiRNA cluster ([[mir-17 microRNA precursor family|miR-17]], [[mir-18 microRNA precursor family|miR-18]], miR-19 and [[mir-20 microRNA precursor family|miR-20]]) increased during the induction of endothelial cell differentiation in embryonic [[stem cell]]s (tested on murine) or induce [[Cell potency|pluripotent]] stem cells. Even though this cluster regulates vascular integrity and [[angiogenesis]], none of each members has a significant impact on the endothelial differentiation of pluripotent stem cells.<ref name="pmid22797777">{{cite journal |author1=Karine Tréguer |author2=Eva-Marie Heinrich |author3=Kisho Ohtani and al. |title=Role of the MicroRNA-17–92 Cluster in the Endothelial Differentiation of Stem Cells |journal=Journal of Vascular Research |volume=49 | issue= 5| pages=447–460 |year=2012 |pmid=22797777 |pmc= |doi=10.1159/000339429 |url=}}</ref>

== miR-19a roles ==

=== Spinocerebellar ataxia type 1 ===
It has been showing that the 3' UTR of the [[ATXN1]] gene contains 3 target sites for miR-19, and this microRNA shows moderate down regulation of [[reporter gene]]s containing the ATXN1 3' UTR. Furthermore, it directly binds to the ATXN1 3´UTR to suppress the translation of ATXN1. ATXN1 is also regulated by [[mir-101 microRNA precursor family|miR-101]], and [[mir-130 microRNA precursor family|miR-130]].<ref name="pmid18758459" />

=== Breast cancer ===

MiR-19 regulates [[tissue factor]] expression at a [[Post-transcriptional regulation|post-transcriptional]] level in [[breast cancer]] cells, providing a molecular basis for the selective expression of the tissue factor gene. Thanks to bioinformatics analyses, scientists predicted microRNA-[[Binding sites]] for miR-19, miR-20 and miR-106b in the 3'-UTR tissue factor transcript. Experiments confirmed that it negatively regulates gene expression in [[MCF-7]] cells, and over-expression of miR-19 [[downregulation|downregulates]] tissue factor expression in [[MDA-MB-231]] cells (human breast cancer cell lines). The main action of miR-19 seems to inhibit protein translation of the tissue factor gene in less invasive breast cancer cells.<ref name="pmid21059650" />

== miR-19b roles ==

=== Rheumatoid arthritis ===
MiR-19 also takes part in [[Inflammation|inflammatory responses]] [[Enhancer (genetics)|enhancing]] or [[Repressor|repressing]] pro-inflammatory mediators expression. It positively regulates [[Toll-like receptor]] signaling with [[DICER1|Dicer1]] deletion and miRNA depletion. MiR-19b is an important protagonist in this phenomenon, regulating positively [[NF-kB]] activity.
MiRNA depletion inhibits [[cytokine]]s production by NF-kB. This indicates that miRNA control of NF-kB signaling repressors thanks to its relief. Some important regulators of NF-kB signaling ([[TNFAIP3|like A20 (Tnfaip3)]], [[CYLD (gene)|Cyld]], and [[OTUD7B|Cézanne (Otud7b)]]) is targeted by the miR-17-92 cluster.<br/>
Moreover, mir-19 targets some members of the Tnfaip3-ubiquitin editing complex ([[TNFAIP3|Tnfaip3]]/[[ITCH|Itch]]/[[TNIP1|Tnip1]]/[[RNF11|Rnf11]]). MiR-19 directly involved in the modulation of several NF-kB signaling negative regulators expression, indicating an important role for Rnf11 in the effect of miR-19b on NF-kB signaling.<br/>
Finally, miR-19b exacerbates the [[Synovial joint|cells crucial]] inflammatory activation in [[Rheumatoid arthritis|rheumatoid arthritis disease]].<ref name="pmc3439911" /><ref name="pmid20505335" />

==References==

{{reflist|30em}}

==Further reading==
{{refbegin | 1}}

*{{Cite journal  | author=Andrea Ventura, Amanda G. Young, Monte M. Winslow and al. | title=Targeted deletion reveals essential and overlapping functions of the miR-17~92 family of miRNA clustersMechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β | journal = Cell | volume = 132 | issue =5 | pages=875–886 | year = 2008 | pmid=18329372 |pmc=2323338 |doi=10.1016/j.cell.2008.02.019 |url=}}
*{{Cite journal  |author1=Lixin Hong |author2=Maoyi Lai |author3=Michelle Chen and al. | title=The miR-17-92 Cluster of microRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence | journal = Cancer Res | volume = 70 | issue =21 | pages=8547–8557 | year =2010 | doi = 10.1158/0008-5472.CAN-10-1938 | pmid=20851997 |pmc=2970743 }}
*{{Cite journal  |author1=JR-Shiuan Yang |author2=Michael D. Phillips |author3=Doron Betel and al. | title=Widespread regulatory activity of vertebrate microRNA* species | journal = RNA | volume = 17 | issue =2 | pages=312–26 | year =2011 | doi = 10.1261/rna.2537911 | pmid=21177881 |pmc=3022280 }}
*{{cite journal |author1=Joost Kluiver |author2=Johan H. Gibcus |author3=Chris Hettinga and al. |title=Rapid Generation of MicroRNA Sponges for MicroRNA Inhibition |journal=PLOS ONE |volume=7 | issue=1 | pages=e29275 |year=2012 |pmid=22238599 |pmc=3253070 |doi=10.1371/journal.pone.0029275 |url=|bibcode=2012PLoSO...729275K }}

==External links==
* {{Rfam|id=RF00245|name=mir-19 microRNA precursor family}}
* [http://www.mirbase.org/cgi-bin/mirna_summary.pl?fam=MIPF0000011 miRBase family entry for miR-19 family]
{{miRNA precursor families}}

[[Category:MicroRNA]]
[[Category:MicroRNA precursor families]]