miR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma

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• 作者：Yingnan Sun (1) (2)
  Shourong Shen (1) (2)
  Xiaoping Liu (3) (4)
  Hailin Tang (3) (4)
  Zeyou Wang (1) (3)
  Zhibin Yu (1) (3)
  Xiayu Li (1) (2)
  Minghua Wu (1) (3)
  
• 关键词：miRNA ; miR ; 429 ; Colorectal carcinoma ; TGF ; β1 ; Snail ; ZEB2
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：390
• 期：1-2
• 页码：19-30
• 全文大小：8,759 KB
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• 作者单位：Yingnan Sun (1) (2)
  Shourong Shen (1) (2)
  Xiaoping Liu (3) (4)
  Hailin Tang (3) (4)
  Zeyou Wang (1) (3)
  Zhibin Yu (1) (3)
  Xiayu Li (1) (2)
  Minghua Wu (1) (3)
  
  1. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, People’s Republic of China
  2. Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People’s Republic of China
  3. Cancer Research Institute; Disease Genome Research Center; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, People’s Republic of China
  4. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China
  
• ISSN：1573-4919

文摘

The 5-year survival rate for colorectal cancer is approximately 55?% because of its invasion and metastasis. The epithelial–mesenchymal transition (EMT) is one of the well-defined processes during the invasion and distant metastasis of primary epithelial tumors. miR-429, a member of the miR-200 family of microRNAs, was previously shown to inhibit the expression of transcriptional repressors ZEB1/delta EF1 and SIP1/ZEB2, and regulate EMT. In this study, we showed that miR-429 was significantly downregulated in colorectal carcinoma (CRC) tissues and cell lines. We found that miR-429 inhibited the proliferation and growth of CRC cells in vitro and in vivo, suggesting that miR-429 could play a role in CRC tumorigenesis. We also showed that downregulation of miR-429 may contribute to carcinogenesis and the initiation of EMT of CRC by targeting Onecut2. Further researches indicated that miR-429 inhibited the cells migration and invasion and reversed TGF-β-induced EMT changes in SW620 and SW480 cells. miR-429 could reverse the change of EMT-related markers genes induced by TGF-β1, such as E-cadherin, CTNNA1, CTNNB1, TFN, CD44, MMP2, Vimentin, Slug, Snail, and ZEB2 by targeting Onecut2. Taken together, our data showed that transcript factor Onecut2 is involved in the EMT, migration and invasion of CRC cells; miR-429 inhibits the initiation of EMT and regulated expression of EMT-related markers by targeting Onecut2; and miR-429 or Onecut2 is the important therapy target for CRC.