miR-421, miR-155 and miR-650: Emerging Trends of Regulation of Cancer and Apoptosis

  • 발행 : 2014.03.01


It is becoming progressively more understandable that between transcription and translation there lies another versatile regulator that quantitatively controls the expression of mRNAs. Identification of miRNAs as key regulators of wide ranging signaling cascades and modulators of different cell-type and context dependent activities attracted basic and clinical scientists to study modes and mechanisms in details. In line with this approach overwhelmingly increasing in vivo and in vitro studies are deepening our understanding regarding miR-421, mir-155 and miR-650 mediated regulation of cellular activities. We also attempt to provide an overview of long non coding RNAs.


  1. Jiang Z, Guo J, Xiao B (2010). Increased expression of miR-421 in human gastric carcinoma and its clinical association. J Gastroenterol, 45, 17-23.
  2. Zhou H, Xiao B, Zhou F, (2012). MiR-421 is a functional marker of circulating tumor cells in gastric cancer patients. Biomarkers, 17, 104-10.
  3. Guo Y, Tian P, Yang C, et al (2013). Silencing the doublestranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion. Pharm Res, [Epub ahead of print].
  4. Hao J, Zhang S, Zhou Y, et al (2011). MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer. Biochem Biophys Res Commun, 406, 552-7.
  5. Herbert KM, Pimienta G, Degregorio SJ, Alexandrov A, Steitz JA (2013). Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. Cell Rep, 5, 1070-81.
  6. Hu H, Du L, Nagabayashi G, Seeger RC, Gatti RA (2010). ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci USA, 107, 1506-11.
  7. Zhang Y, Wei W, Cheng N, et al (2012). Hepatitis C virusinduced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology, 56, 1631-40.
  8. Zhang Z, Zhu Z, Watabe K, et al (2013). Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ, 20, 1558-68.
  9. Zhao XD, Zhang W, Liang HJ, Ji WY (2013). Overexpression of miR -155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting SOCS1 and STAT3. PLoS One, 8, 56395.
  10. Zheng SR, Guo GL, Zhai Q, Zou ZY, Zhang W (2013). Effects of miR-155 antisense oligonucleotide on breast carcinoma cell line MDA-MB-157 and implanted tumors. Asian Pac J Cancer Prev, 14, 2361-6.
  11. Zhong XY, Yu JH, Zhang WG, et al (2012). MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression. Gene, 493, 44-51.
  12. Bertozzi D, Marinello J, Manzo SG, et al (2014). The natural inhibitor of DNA topoisomerase i, camptothecin, modulates HIF-$1\alpha$ activity by changing miR expression patterns in human cancer cells. Mol Cancer Ther, 13, 239-48.
  13. Alachkar H, Santhanam R, Harb JG (2013). Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia. J Hematol Oncol, 6, 21.
  14. Babar IA, Cheng CJ, Booth CJ, et al (2012). Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci USA, 109, 1695-704.
  15. Bai Y, Qiu GR, Zhou F, et al (2013). Overexpression of DICER1 induced by the upregulation of GATA1 contributes to the proliferation and apoptosis of leukemia cells. Int J Oncol, 42,1317-24.
  16. Chaulk SG, Lattanzi VJ, Hiemer SE, Fahlman RP, Varelas X (2013). The Hippo Pathway Effectors TAZ/YAP regulate dicer expression and miRNA biogenesis through Let-7. J Biol Chem, 289, 1886-91.
  17. Chen L, Tang Y, Wang J, Yan Z, Xu R (2013). miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4. Biochem Biophys Res Commun, 435, 745-50.
  18. Chiyomaru T, Yamamura S, Fukuhara S, et al (2013). Genistein inhibits prostate cancer cell growth by targeting miR-34a and Oncogenic HOTAIR. PLoS One, 8, 70372.
  19. Feng L, Xie Y, Zhang H, Wu Y (2011). Down-regulation of NDRG2 gene expression in human colorectal cancer involves promoter methylation and microRNA-650. Biochem Biophys Res Commun, 406, 534-8.
  20. Gomez-Cabello D, Adrados I, Gamarra D, et al (2013). DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts. Aging Cell, 12, 923-31.
  21. Neilsen PM, Noll JE, Mattiske S, et al (2013). Mutant p53 drives invasion in breast tumors through up-regulation of miR-155. Oncogenem, 32, 2992-3000.
  22. Liu WJ, Zhao YP, Zhang TP, et al (2003). MLH1 as a Direct Target of MiR-155 and a Potential Predictor of Favorable Prognosis in Pancreatic Cancer. J Gastrointest Surg, 17, 1399-405.
  23. Mansour WY, Bogdanova NV, Kasten-Pisula U, et al (2013). Aberrant overexpression of miR-421 downregulates ATM and leads to a pronounced DSB repair defect and clinical hypersensitivity in SKX squamous cell carcinoma. Radiother Oncol, 106, 147-54.
  24. Mraz M, Dolezalova D, Plevova K, et al (2012). MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia. Blood, 119, 2110-3.
  25. Pu J, Bai D, Yang X, et al (2012). Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155. Biochem Biophys Res Commun, 428, 210-5.
  26. Qin W, Ren Q, Liu T, Huang Y, Wang J. MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1. FEBS Lett, 587, 1434-9.
  27. Rozovski U, Calin GA, Setoyama T, et al (2012). Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells. Mol Cancer, 12, 50.
  28. Sandhu SK, Volinia S, Costinean S, et al (2012). miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the $E\mu$-miR-155 transgenic mouse model. Proc Natl Acad Sci USA, 109, 20047-52.
  29. Sun M, Xia R, Jin F, et al (2013). Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumour Biol, 35, 1065-73.
  30. Johansson J, Berg T, Kurzejamska E, et al (2013). MiR-155-mediated loss of C/$EBP\beta$shifts the TGF-$\beta$ response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer. Oncogene.
  31. Zhang X, Li M, Zuo K, et al (2013). Upregulated miR-155 in papillary thyroid carcinoma promotes tumor growth by targeting APC and activating Wnt/$\beta$-Catenin signaling. J Clin Endocrinol Metab, 98, 1305-13.
  32. Zhang X, Zhu W, Zhang J, et al (2010). MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity. Biochem Biophys Res Commun, 395, 275-80.
  33. Zhang Y, Gong W, Dai S, et al (2012). Downregulation of human farnesoid X receptor by miR-421 promotes proliferation and migration of hepatocellular carcinoma cells. Mol Cancer Res, 10, 516-22.
  34. Kong W, Yang H, He L, et al (2008). MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol, 28, 6773-84.
  35. Kopp KL, Ralfkiaer U, Gjerdrum LM, et al (2013). STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma. Cell Cycle, 12, 1939-47.
  36. Li P, Grgurevic S, Liu Z, et al (2013). Signal transducer and activator of transcription-3 induces MicroRNA-155 expression in chronic lymphocytic leukemia. PLoS One, 8, 64678.
  37. Ling N, Gu J, Lei Z, et al (2013). micro RNA-155 regulates cell proliferation and invasion by targeting FOXO3a in glioma. Oncol Rep, 30, 2111-8.
  38. Liu Q, Chen J, Wang J, et al (2013). Putative tumor suppressor gene SEL1L was downregulated by aberrantly upregulated hsa-mir-155 in human pancreatic ductal adenocarcinoma. Mol Carcinog, [Epub ahead of print].
  39. Tang X, Wen S, Zheng D, ET AL (2013). Acetylation of drosha on the N-terminus inhibits its degradation by ubiquitination. PLoS One, 8, 72503.
  40. Xhemalce B, Robson SC, Kouzarides T (2012). Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell, 151, 278-88.
  41. Xu TP, Zhu CH, Zhang J, et al (2013). MicroRNA-155 expression has prognostic value in patients with non-small cell lung cancer and digestive system carcinomas. Asian Pac J Cancer Prev, 14, 7085-90.
  42. Yang L, Lin C, Jin C, et al (2013), Rosenfeld MG. lncRNAdependent mechanisms of androgen-receptor-regulated gene activation programs. Nature, 500, 598-602.
  43. Yang X, Song JH, Cheng Y, et al (2013). Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells. Gut.
  44. Yao Q, Sun JG, Ma H, et al (2014;). Monitoring microRNAs using a molecular beacon in CD133+/ CD338+ human lung adenocarcinoma-initiating A549 Cells. Asian Pac J Cancer Prev, 15, 161-6.
  45. Zeng ZL, Li FJ, Gao F, Sun DS, Yao L (2013). Upregulation of miR-650 is correlated with down-regulation of ING4 and progression of hepatocellular carcinoma. J Surg Oncol, 107, 105-10.
  46. Zhang C, Zhao J, Deng H (2013). $17\beta$-estradiol up-regulates miR-155 expression and reduces TP53INP1 expression in MCF-7 breast cancer cells. Mol Cell Biochem, 379, 201-11.
  47. Zhang GJ, Xiao HX, Tian HP, et al (2013). Upregulation of microRNA-155 promotes the migration and invasion of colorectal cancer cells through the regulation of claudin-1 expression. Int J Mol Med, 31, 1375-80.

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