The roles of miR-200c in colon cancer and associated molecular mechanisms

详细信息    查看全文

• 作者：Jianmei Chen (1)
  Weining Wang (2)
  Yangde Zhang (1)
  Tiehui Hu (1)
  Yuxiang Chen (1)
  
• 关键词：Colon cancer ; miR ; 200c ; Apoptosis ; Metastasis ; PTEN ; p53 ; PP1
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：July 2014
• 年：2014
• 卷：35
• 期：7
• 页码：6475-6483
• 全文大小：659 KB
• 参考文献：1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22:191鈥?. CrossRef
  2. Xu AG, Yu ZJ, Jiang B, Wang XY, Zhong XH, Liu JH, et al. Colorectal cancer in Guangdong Province of China: a demographic and anatomic survey. World J Gastroenterol. 2010;16:960鈥?. CrossRef
  3. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2013;S0140鈥?736:61649鈥?.
  4. Boominathan L. The tumor suppressors p53, p63, and p73 are regulators of microRNA processing complex. PLoS One. 2010;5:e10615. CrossRef
  5. Li J, Chen Y, Zhao J, Kong F, Zhang Y. miR-203 reverses chemoresistance in p53-mutated colon cancer cells through downregulation of Akt2 expression. Cancer Lett. 2011;304:52鈥?. CrossRef
  6. Wang Y, Lee CG. MicroRNA and cancer鈥攆ocus on apoptosis. J Cell Mol Med. 2009;13:12鈥?3. CrossRef
  7. Xiong J, Du Q, Liang Z. Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein. Oncogene. 2010;29:4980鈥?. CrossRef
  8. Dassow H, Aigner A. MicroRNAs (miRNAs) in colorectal cancer: from aberrant expression towards therapy. Curr Pharm Des. 2013;19:1242鈥?2.
  9. Baffa R, Fassan M, Volinia S, O鈥橦ara B, Liu CG, Palazzo JP, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214鈥?1. CrossRef
  10. Wang M, Zhang P, Li Y, Liu G, Zhou B, Zhan L, et al. The quantitative analysis by stem-loop real-time PCR revealed the microRNA-34a, microRNA-155 and microRNA-200c overexpression in human colorectal cancer. Med Oncol. 2012;29:3113鈥?. CrossRef
  11. Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, et al. Prognostic values of microRNAs in colorectal cancer. Biomark Insights. 2006;2:113鈥?1.
  12. Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2013 Aug 26. [Epub ahead of print].
  13. Chen J, Wang W, Zhang Y, Chen Y, Hu T. Predicting distant metastasis and chemoresistance using plasma miRNAs. 2014;31:799.
  14. Ota T, Doi K, Fujimoto T, Tanaka Y, Ogawa M, Matsuzaki H, et al. KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells. Anticancer Res. 2012;32:2271鈥?.
  15. Chen ML, Liang LS, Wang XK. miR-200c inhibits invasion and migration in human colon cancer cells SW480/620 by targeting ZEB1. Clin Exp Metastasis. 2012;29:457鈥?9. CrossRef
  16. Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, Koike J, et al. MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut. 2013;62:1315鈥?6. CrossRef
  17. Bai M, Zhu X, Zhang Y, Zhang S, Zhang L, Xue L, et al. Abnormal hippocampal BDNF and miR-16 expression is associated with depression-like behaviors induced by stress during early life. PLoS One. 2012;7:e46921. CrossRef
  18. Zhang X, Kon T, Wang H, Li F, Huang Q, Rabbani ZN, et al. Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha. Cancer Res. 2004;64:8139鈥?2. CrossRef
  19. Yamada T, Sato K, Komachi M, Malchinkhuu E, Tobo M, Kimura T, et al. Lysophosphatidic acid (LPA) in malignant ascites stimulates motility of human pancreatic cancer cells through LPA1. J Biol Chem. 2004;279:6595鈥?05. CrossRef
  20. Komachi M, Tomura H, Malchinkhuu E, Tobo M, Mogi C, Yamada T, et al. LPA1 receptors mediate stimulation, whereas LPA2 receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites. Carcinogenesis. 2009;30:457鈥?5. CrossRef
  21. Scatena CD, Kumer JL, Arbitrario JP, Howlett AR, Hawtin RE, Fox JA, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010;66:881鈥?. CrossRef
  22. Zhang X, Li Y, Huang Q, Wang H, Yan B, Dewhirst MW, et al. Increased resistance of tumor cells to hyperthermia mediated by integrin-linked kinase. Clin Cancer Res. 2003;9:1155鈥?0.
  23. Li DW, Liu JP, Schmid PC, Schlosser R, Feng H, Liu WB, et al. Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities. Oncogene. 2006;25:3006鈥?2. CrossRef
  24. Iiizumi M, Liu W, Pai SK, Furuta E, Watabe K. Drug development against metastasis-related genes and their pathways: a rationale for cancer therapy. Biochim Biophys Acta. 2008;1786:87鈥?04.
  25. Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, et al. Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res. 2011;17:3029鈥?8. CrossRef
  26. Ahmed D, Eide PW, Eilertsen IA, Danielsen SA, Ekn忙s M, Hektoen M, et al. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2013;2:e71. CrossRef
  27. Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, et al. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev. 1999;13:152鈥?. CrossRef
  
• 作者单位：Jianmei Chen (1)
  Weining Wang (2)
  Yangde Zhang (1)
  Tiehui Hu (1)
  Yuxiang Chen (1)
  
  1. Hepatobiliary and Enteric Surgery Research Center Xiangya Hospital, Central South University, Changsha, 410008, China
  2. Department of Gastroenterology, First Hospital of Changsha City, Changsha, 410008, China
  
• ISSN：1423-0380

文摘

The expression of miR-200c has been widely reported to be elevated in tumor tissues and sera of patients with colorectal cancer (CRC) and has been found to correlate with poor prognosis. However, how miR-200c regulates the apoptosis, survival, invasion, metastasis, and tumor growth in colon cancer cells remains to be fully elucidated. This study seeks to further investigate the role of miR-200c in colon cancer development. The expression of miR-200c in tumor and peritumoral tissues of 101 colon cancer patients was measured by real-time PCR. miR-200c expression in HCT-116 and HT-29 colon cancer cells was silenced by adenovirus-carried expression of antisense mRNA against miR-200c. The protein levels of PTEN, p53 Ser15, PP1, and activated caspase-3 in HCT-116 and HT-29 cells were measured by Western blot. This study demonstrated that the expression of miR-200c was significantly higher in tumor tissues than in peritumoral tissues of colon cancer patients. The elevated miR-200c expression significantly correlated with the TNM stage, lymph node metastasis, and invasion of colon cancer. Silencing miR-200c expression significantly induced cell apoptosis, inhibited long-term survival, invasion, and metastasis, and delayed xenograft tumor growth. Importantly, silencing miR-200c expression sensitized the therapeutic effect of Ara-C (Cytarabine). The effects of silencing miR-200c expression were associated with upregulation of PTEN protein and p53 Ser15 phosphorylation levels in HCT-116 cells and PTEN protein expression in HT-29 cells. In conclusion, miR-200c functions as an oncogene in colon cancer cells through regulating tumor cell apoptosis, survival, invasion, and metastasis as well as xenograft tumor growth through inhibition of PTEN expression and p53 phosphorylation.