miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer

Our previous studies reported that miR-451 could protect against erythroid oxidant stress target gene-Ywhaz (14-3-3zeta) via inhibiting FoxO3 in the erythropoiesis. This study aimed to investigate the potential mechanism underlying the regulatory effect of miR-451 on human colorectal cancer (CRC) ce...

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Published inAmerican journal of translational research Vol. 7; no. 12; pp. 2775 - 2785
Main Authors Li, Yaoyao, Wang, Jijun, Dai, Xiaorong, Zhou, Zhengbin, Liu, Jing, Zhang, Yu, Li, Yan, Hou, Yaying, Pang, Lei, Wang, Xiaohong, Wang, Chenhai, Hao, Zhenfeng, Zhang, Yanqing, Jiang, Jixin, Cheng, Hongwei, Yu, Duonan
Format Journal Article
LanguageEnglish
Published United States e-Century Publishing Corporation 01.01.2015
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Summary:Our previous studies reported that miR-451 could protect against erythroid oxidant stress target gene-Ywhaz (14-3-3zeta) via inhibiting FoxO3 in the erythropoiesis. This study aimed to investigate the potential mechanism underlying the regulatory effect of miR-451 on human colorectal cancer (CRC) cells. In this study, expressions of miR-451 and Ywhaz in CRC tissues and adjacent normal tissues were detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry respectively. Human colon cancer cell lines were transfected with miR-451-MSCV-PIG retroviral vector to restore miR-451 expression. Ywhaz-3'UTR luciferase reporter assay confirmed Ywhaz as a direct target gene of miR-451. HCT116 cells and H29 cells were transfected with -shRNA-Ywhaz (pSGU6-Ywahz-shRNA-GFP) and the protein level of FoxO3 in the nucleus and cytoplasm was detected via Western blot assay. The anti-tumor effects of miR-451 were further verified in nude mice. miR-451 was significantly down-regulated in human colon cancer tissues and cell lines (HCT116 and HT29), and inversely correlated with Dukes stage of colon cancer. Ywhaz was a candidate target gene of miR-451 and able to stimulate tumor growth via binding to FoxO3, inhibiting the FoxO3 nuclear accumulation. miR-451 may inhibit the colon cancer growth in vitro and in vivo, likely through directly targeting Ywhaz and indirectly regulating the nuclear accumulation of FoxO3.
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ISSN:1943-8141
1943-8141