Biology:mir-200
| mir-200 | |
|---|---|
 miR-200 microRNA secondary structure and sequence conservation | |
| Identifiers | |
| Symbol | mir-200 |
| Rfam | RF00982 |
| miRBase family | MIPF0000019 |
| NCBI Gene | 406983 |
| HGNC | 31578 |
| OMIM | 612090 |
| Other data | |
| RNA type | microRNA |
| Domain(s) | Eukaryota; Chordata; |
| PDB structures | PDBe |
In molecular biology, the miR-200 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by binding and cleaving mRNAs or inhibiting translation. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141, and miR-429. There is growing evidence to suggest that miR-200 microRNAs are involved in cancer metastasis.[1]
Genomic location
The five members of miR-200 are found in two clusters. In humans, miR-200a, miR-200b, and miR-429 are located on chromosome 1 and miR-200c and miR-141 are on chromosome 12. In mice, the two clusters are on chromosomes 4 and 6.[1]
Expression and epigenetic regulation
Members of the miR-200 family are highly enriched in epithelial tissues.[2] While the mir-200 family is highly expressed in normal epithelial cells, it is not expressed in normal fibroblast cells that are of mesenchymal origin. The expression in mesenchymal cells is repressed by epigenetic marks and each cluster is repressed by a different mark. While the promoter of the cluster on chromosome 1 is occupied by polycomb specific mark H3K27me3, the promoter of the cluster on chromosome 12 is repressed by DNA methylation.[3] DNA methylation of the mir-200c/mir-141 promoter occurs aberrantly in certain aggressive carcinoma cells that are of epithelial origin, but have undergone epithelial to mesenchymal transition and have the mir-200 family silenced.[4]
Association with tumour progression
The miR-200 family is believed to play an essential role in tumor suppression by inhibiting epithelial-mesenchymal transition (EMT), the initiating step of metastasis (Korpal). EMT occurs as part of embryonic development, and shares many similarities with cancer progression. During EMT, cells lose adhesion and increase in motility. This is characterized by repression of E-cadherin expression, which also occurs during the initial stages of metastasis.
By contrast, miR-200 has been shown to promote the last step of metastasis in which migrating cancer cells undergo MET during their colonization at distant tissues. In a series of mouse mammary isogenic cancer cell lines, the miR-200 family is highly expressed only in the cells that are able to form metastases (4T1 cells) but not in other cells which are unable to colonize (4TO7 cells). Overexpression of miR-200c in non-metastatic 4TO7 cells readily enables MET and colonization of the liver and lung.[5]
MiR-200 targets the E-cadherin transcriptional repressors ZEB1 and ZEB2. Knockdown of miR-141 and miR-200b has been shown to reduce E-cadherin expression thus increasing cell motility and inducing EMT.[6][7] Consistent with these findings, overexpression of miR-200b resulted in a decrease of endometriotic cell motility and invasive growth, associated with ZEB1 and ZEB2 downregulation and E-cadherin upregulation.[8] Note that family members of miR-200 may have different functions due to differences in their seed regions: miR-200bc share the same seed region, while miR-200a has one nucleotide change.[9]
Cancer
The role of miR-200 in EMT and tumor progression has been linked to several cancers including:
- Bladder cancer[10][11]
- Breast cancer[12][13]
- Melanoma[14]
- Ovarian cancer[15]
- Pancreatic cancer[16]
- Prostate cancer[17]
- Stomach cancer[18]
- Lung cancer[19]
- Colorectal cancer: MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients.[20]
References
- ↑ 1.0 1.1 "The miR-200 family inhibits epithelial-mesenchymal transition (EMT) and promotes mesenchymal-epithelial transition (MET) by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2". J. Biol. Chem. 283 (22): 14910–4. May 2008. doi:10.1074/jbc.C800074200. PMID 18411277.
- ↑ "MicroRNA expression profiles classify human cancers". Nature 435 (7043): 834–8. June 2005. doi:10.1038/nature03702. PMID 15944708. Bibcode: 2005Natur.435..834L.
- ↑ Vrba, L; Garbe, JC; Stampfer, MR; Futscher, BW (2011). "Epigenetic regulation of normal human mammary cell type-specific miRNAs.". Genome Research 21 (12): 2026–37. doi:10.1101/gr.123935.111. PMID 21873453.
- ↑ Vrba, L; Jensen, TJ; Garbe, JC; Heimark, RL; Cress, AE; Dickinson, S; Stampfer, MR; Futscher, BW (2010). "Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells.". PLOS ONE 5 (1): e8697. doi:10.1371/journal.pone.0008697. PMID 20084174. Bibcode: 2010PLoSO...5.8697V.
- ↑ Dykxhoorn DM (2010). "MicroRNAs and metastasis: little RNAs go a long way". Cancer Res 70 (16): 6401–6406. doi:10.1158/0008-5472.CAN-10-1346. PMID 20663901.
- ↑ "The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1". Nat. Cell Biol. 10 (5): 593–601. May 2008. doi:10.1038/ncb1722. PMID 18376396.
- ↑ "The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2". Genes Dev. 22 (7): 894–907. April 2008. doi:10.1101/gad.1640608. PMID 18381893.
- ↑ Eggers, Julia (2016). "microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4.". Reproductive Biomedicine Online 32 (4): 434–45. doi:10.1016/j.rbmo.2015.12.013. PMID 26854065. https://www.rbmojournal.com/article/S1472-6483(16)00009-2/fulltext.
- ↑ Uhlmann, S; Zhang, JD; Schwäger, A; Mannsperger, H; Riazalhosseini, Y; Burmester, S; Ward, A; Korf, U et al. (29 July 2010). "miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer.". Oncogene 29 (30): 4297–306. doi:10.1038/onc.2010.201. PMID 20514023.
- ↑ "miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy". Clin. Cancer Res. 15 (16): 5060–72. August 2009. doi:10.1158/1078-0432.CCR-08-2245. PMID 19671845.
- ↑ "Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer". Int J Cancer 128 (6): 1327–34. May 2010. doi:10.1002/ijc.25461. PMID 20473948.
- ↑ "E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells". Int. J. Cancer 126 (11): 2575–83. June 2010. doi:10.1002/ijc.24972. PMID 19839049.
- ↑ Blagosklonny, Mikhail V., ed (2009). "miR-200 enhances mouse breast cancer cell colonization to form distant metastases". PLOS ONE 4 (9): e7181. doi:10.1371/journal.pone.0007181. PMID 19787069. Bibcode: 2009PLoSO...4.7181D.
- ↑ Elson-Schwab, I; Lorentzen, A; Marshall, CJ (2010). Danen, Erik H. J.. ed. "MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion". PLOS ONE 5 (10): e13176. doi:10.1371/journal.pone.0013176. PMID 20957176. Bibcode: 2010PLoSO...513176E.
- ↑ "A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer.". Gynecol Oncol 114 (3): 457–64. 2009. doi:10.1016/j.ygyno.2009.05.022. PMID 19501389.
- ↑ "Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells.". Cancer Res 69 (16): 6704–12. 2009. doi:10.1158/0008-5472.CAN-09-1298. PMID 19654291.
- ↑ "miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells.". Stem Cells 27 (8): 1712–21. 2009. doi:10.1002/stem.101. PMID 19544444.
- ↑ "Downregulation of microRNA-200 in EBV-associated gastric carcinoma.". Cancer Res 70 (11): 4719–27. 2010. doi:10.1158/0008-5472.CAN-09-4620. PMID 20484038.
- ↑ "Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.". Genes Dev 23 (18): 2140–51. 2009. doi:10.1101/gad.1820209. PMID 19759262.
- ↑ Pichler, M; Ress, A. L.; Winter, E; Stiegelbauer, V; Karbiener, M; Schwarzenbacher, D; Scheideler, M; Ivan, C et al. (2014). "MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients". British Journal of Cancer 110 (6): 1614–21. doi:10.1038/bjc.2014.51. PMID 24504363.
Further reading
- "The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.". Nat Cell Biol 10 (5): 593–601. 2008. doi:10.1038/ncb1722. PMID 18376396.
- "Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.". Mol Cell 39 (5): 761–72. 2010. doi:10.1016/j.molcel.2010.08.013. PMID 20832727.
- "The ZEB/miR-200 feedback loop--a motor of cellular plasticity in development and cancer?". EMBO Rep 11 (9): 670–7. 2010. doi:10.1038/embor.2010.117. PMID 20706219.
- "The role of the miR-200 family in epithelial-mesenchymal transition.". Cancer Biol Ther 10 (3): 219–22. 2010. doi:10.4161/cbt.10.3.12548. PMID 20592490.
- "Differential expression of the miR-200 family microRNAs in epithelial and B cells and regulation of Epstein-Barr virus reactivation by the miR-200 family member miR-429.". J Virol 84 (15): 7892–7. 2010. doi:10.1128/JVI.00379-10. PMID 20484493.
- Teleman AA (2010). "miR-200 de-FOGs insulin signaling.". Cell Metab 11 (1): 8–9. doi:10.1016/j.cmet.2009.12.004. PMID 20085731.
- "Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K.". Cell 139 (6): 1096–108. 2009. doi:10.1016/j.cell.2009.11.020. PMID 20005803.
- "Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition.". Gynecol Oncol 116 (1): 117–25. 2010. doi:10.1016/j.ygyno.2009.08.009. PMID 19854497.
- "The miR-200 family: central player for gain and loss of the epithelial phenotype.". Gastroenterology 136 (5): 1835–7. 2009. doi:10.1053/j.gastro.2009.03.009. PMID 19324106.
- Peter ME (2009). "Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression.". Cell Cycle 8 (6): 843–52. doi:10.4161/cc.8.6.7907. PMID 19221491.
- "The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis.". RNA Biol 5 (3): 115–9. 2008. doi:10.4161/rna.5.3.6558. PMID 19182522.
- "The microRNA-200 family regulates epithelial to mesenchymal transition.". ScientificWorldJournal 8: 901–4. 2008. doi:10.1100/tsw.2008.115. PMID 18836656.
- "A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition.". Cancer Res 68 (19): 7846–54. 2008. doi:10.1158/0008-5472.CAN-08-1942. PMID 18829540.
- "A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells.". EMBO Rep 9 (6): 582–9. 2008. doi:10.1038/embor.2008.74. PMID 18483486.
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