MIR145 (microRNA 145)

2012-02-01   Mohit Sachdeva , Yin Yuan Mo 

Department of Radiation Oncology, Duke University Medical center, Durham, North Carolina-27710, USA (MS); Department of Medical Microbiology, Immunology, Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA (YYM)

Identity

HGNC
LOCATION
5q32
LOCUSID
ALIAS
MIRN145,miR-145,miRNA145

DNA/RNA

Atlas Image
Figure 1: A) Genomic localization of miR-145 gene on chromosome 5q32. B) Stem-loop structure of miR-145 (Red: mature miR-145 sequence).

Description

miR-145 is located on chromosome 5 (5q32-33) within a 4.09 kb region (miRBase). The pri-microRNA structure of miR-145 has not been identified, yet it is suggested that it co-transcribed with miR-143. This gene has been implicated as both tumor and metastasis suppressor in multiple tumor types (Sachdeva and Mo, 2010a).

Transcription

miR-145 is transcribed by RNA pol-II into pri-miRNA sequence, which is first processed to pre-miRNA (~88 bp long) involving RNA cutting and exporting, and finally to mature miR-145. miR-145 is a p53-regulated gene. Several reports suggest that miR-145 can be induced transcriptionally by p53 in response to stress such as serum starvation or anticancer drugs (Sachdeva et al., 2009; Spizzo et al., 2010). Interestingly, another report showed a novel mechanism of posttranscriptional regulation of miR-145 that occurs via p53-mediated RNA processing (Suzuki et al., 2009). Recently, a study demonstrates that activated Ras can suppress miR-143/145 cluster through Ras-responsive element-binding protein (RREB1), which represses the miR-143/145 promoter (Kent et al., 2010).

Pseudogene

There is no pseudogene reported for this gene.

Proteins

Note

Non-coding RNA.

Implicated in

Entity name
Cancer
Note
Downregulation of miR-145 has been found in cancers of many tissue types including colon, breast, prostate, pancreas, etc. (Sachdeva et al., 2009; Bandres et al., 2006; Michael et al., 2003). For example, in situ hybridization detected accumulation of miR-145 in normal colon epithelia with no signal from adenocarcinomas cells. Loss of miR-145 in various tumors suggests its role as a tumor suppressor. In fact, miR-145 has been well documented as a tumor suppressor gene in multiple tumor types because of its anti-proliferative and pro-apoptotic effects. It is shown that miR-145 can negatively regulate multiple oncogenes such as MYC, Kras, IRS-1, ERK5, etc. involved in cell proliferation and survival (Sachdeva et al., 2009; Kent et al., 2010; Shi et al., 2007; Ibrahim et al., 2011).
Entity name
Metastasis
Note
Several reports suggest that miR-145 is a suppressor of metastasis. For example, mir-145 negatively regulates MUC1 and suppresses invasion and metastasis of the breast cancer cells (Sachdeva and Mo, 2010b). Similar findings in prostate cancer and in gliomas have further confirmed the role of miR-145 as a metastasis suppressor by targeting genes including FASCN1 and SOX2, respectively (Fang et al., 2011; Watahiki et al., 2011; Leite et al., 2011).
Entity name
Stem cells and differentiation
Note
A study has shown that miR-145 is induced during differentiation, and it directly silences the stem cell self renewal and pluripotency program by suppressing multiple pluripotent genes such as OCT4, SOX2 and KLF4 (Xu et al., 2009).
Entity name
Vascular smooth muscle cells
Note
The role of miR-145 in differentiation of vascular smooth muscle cell (VSMC) has been recently investigated. A report demonstrated that miR-145 is the most enriched microRNA in arteries and its expression is significantly downregulated in vascular walls with neointimal lesions (Chen et al., 2004). Similarly, another group, using transgenic mouse model with miR-145 promoter fused to β-galactosidase gene, found that miR-145 is cardiac-specific and smooth-muscle specific microRNA regulated by serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) (Cordes et al., 2009). Further evidence from the miR-43/miR-145 KO rats suggests that this microRNA cluster is expressed mostly in the SMC compartment in vessels and SMC-containing organs and their loss induces an incomplete differentiation of VSMCs (Elia et al., 2009).
Entity name
Note
A comprehensive study using clinical samples combined with mouse models have found that deletion of chromosome 5q correlates with loss of two miRNAs that are abundant in hematopoietic stem/progenitor cells (HSPCs), miR-145 and miR-146a. In addition, they observed that miR-145 is highly expressed in primitive lin- (mouse) and CD34+ (human) bone marrow cells than committed cells and stable knockdown of miR-145 in these cells in mouse marrow results in 5-q syndrome (Starczynowski et al., 2010). Similar work from another group in patients with del (5q) have decreased expression of miR-145 and increased expression of Fli-1 (Kumar et al., 2011). They found that miR-145 functions through repression of Fli-1, a megakaryocyte and erythroid regulatory transcription factor and thus, cells lacking miR-145 have impaired megakaryocyte and erythroid differentiation.

Bibliography

Pubmed IDLast YearTitleAuthors
168542282006Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues.Bandrés E et al
146575042004MicroRNAs modulate hematopoietic lineage differentiation.Chen CZ et al
195783582009miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.Cordes KR et al
167781822006Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing.Diederichs S et al
198165082009The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease.Elia L et al
212110352011The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis.Fang X et al
216905662011MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma.Ibrahim AF et al
211598162010Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.Kent OA et al
218735452011Coordinate loss of a microRNA and protein-coding gene cooperate in the pathogenesis of 5q- syndrome.Kumar MS et al
218805142013MicroRNA expression profiles in the progression of prostate cancer--from high-grade prostate intraepithelial neoplasia to metastasis.Leite KR et al
145737892003Reduced accumulation of specific microRNAs in colorectal neoplasia.Michael MZ et al
199962882010MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1.Sachdeva M et al
178271562007Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells.Shi B et al
197304442010miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells.Spizzo R et al
198984892010Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype.Starczynowski DT et al
196261152009Modulation of microRNA processing by p53.Suzuki HI et al
219803682011MicroRNAs associated with metastatic prostate cancer.Watahiki A et al
194096072009MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells.Xu N et al

Other Information

Locus ID:

NCBI: 406937
MIM: 611795
HGNC: 31532
Ensembl: ENSG00000276365
miRBase:

Variants:

dbSNP: 406937
ClinVar: 406937
TCGA: ENSG00000276365
COSMIC: MIR145

RNA/Proteins

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206

References

Pubmed IDYearTitleCitations
194096072009MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells.447
223273662012Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs.393
199962882010MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1.139
211598162010Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.132
216731062011down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4.105
203827292010EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.102
197304442010miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells.101
210921882010miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc.95
223896282012p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells.88
212894832011MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1.84

Citation

Mohit Sachdeva ; Yin Yuan Mo

MIR145 (microRNA 145)

Atlas Genet Cytogenet Oncol Haematol. 2012-02-01

Online version: http://atlasgeneticsoncology.org/gene/50927/mir145