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Am J Transl Res. 2015 Dec 15;7(12):2775-85. eCollection 2015.

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

Author information

1
Non-Coding RNA Center, Medical College of Yangzhou UniversityYangzhou, Jiangsu 225001, China; Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou UniversityTaixing, Jiangsu 225001, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou UniversityYangzhou, Jiangsu 225001, China.
2
Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
3
Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou University Taixing, Jiangsu 225001, China.
4
Department of Pathology, Subei People's Hospital of Jiangsu Province Affiliated to Yangzhou University Yangzhou 225001, China.
5
Non-Coding RNA Center, Medical College of Yangzhou UniversityYangzhou, Jiangsu 225001, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou UniversityYangzhou, Jiangsu 225001, China; Institute of Comparative Medicine, Yangzhou UniversityYangzhou 225001, China.

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.

KEYWORDS:

Colorectal cancer; FoxO3; Ywhaz (14-3-3zeta); microRNA-451

PMID:
26885274
PMCID:
PMC4731674

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