c-MYC-Regulated miRNA-92b Inhibits Expression of The E3 Ligase FBXW7 in Colorectal Cancer

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c-MYC-Regulated miRNA-92b Inhibits Expression of The E3 Ligase FBXW7 in Colorectal Cancer
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Affiliation:State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University,State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine,State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
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Fund Project:This work was supported by grants from the Sichuan Science and Technology Project (2013ZZ0004), the Shanghai Institutes for Biological Science, Chinese Academy of Sciences & the Sichuan Huiyang Life Science and Technology Corp. Research Program (Y363S21763), National Basic Research Program of China (2011CB510104) and a Zhejiang Sci-Tech University Grant (1204807-Y)

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Abstract:

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Many microRNAs (miRNAs) have been reported to be abnormally expressed in CRC. Recent studies have identified miR-92b as a potential oncogene in several types of cancer. However, the role of miR-92b in CRC has not been clarified. This study aimed to elucidate the role of miR-92b in CRC progression. Relative quantitative PCR revealed that miR-92b expression was significantly increased in human CRC tissues compared to the adjacent tissues. Overexpression of miR-92b in the colorectal cancer cell line SW620 substantially increased cell viability in vitro and xenograft tumor growth in vivo. Also, miR-92b was identified as a secreted miRNA, which can be detected in both cultured medium and the peripheral blood of xenograft mice. Furthermore, we demonstrated that c-MYC, which was also elevated in CRC tissues, promoted the transcription of miR-92b by regulating its promoter activity. Luciferase assay and Western blot analysis revealed that FBXW7 was a novel target of miR-92b and can be negatively regulated by c-MYC. As FBXW7 is a major E3 ligase of c-MYC, our data suggested a potential positive regulatory feedback loop among c-MYC, miR-92b and FBXW7 in CRC. Collectively, we partly provided evidence on how miR-92b is regulated and the potential implications of miR-92b in CRC diagnosis.

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YIN Xiao-Fei, WU Shuai, YANG Yuan-Qin, FANG Xian-Long, XU Hai-Neng, LIU Xin-Yuan, ZHENG Shu, ZHANG Kang-Jian. c-MYC-Regulated miRNA-92b Inhibits Expression of The E3 Ligase FBXW7 in Colorectal Cancer[J]. Progress in Biochemistry and Biophysics,2016,43(7):673-683

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Received:April 14,2016
Revised:June 08,2016
Accepted:June 16,2016
Online: July 19,2016
Published: July 20,2016

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