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miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer
- Publication Year :
- 2015
- Publisher :
- e-Century Publishing Corporation, 2015.
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Abstract
- Background and objective: 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. Methods: 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. Results: 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. Conclusion: 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.
- Subjects :
- Original Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid..........0e9646bb7ad56a7112b1fe55a98d7872