title: miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou University Taixing, Jiangsu 225001, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou University Taixing, Jiangsu 225001, China.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou University Taixing, Jiangsu 225001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Yaying
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pang
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Chenhai
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou University Taixing, Jiangsu 225001, China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Hao
authors.affiliation: Non-Coding RNA Center, Medical College of Yangzhou University Yangzhou, Jiangsu 225001, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Subei People's Hospital of Jiangsu Province Affiliated to Yangzhou University Yangzhou 225001, China.
authors.forename: Jixin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Taixing People's Hospital Affiliated to Yangzhou University Taixing, Jiangsu 225001, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Duonan
authors.initials: D
authors.lastname: Yu
keywords: Colorectal cancer; FoxO3; Ywhaz (14-3-3zeta); microRNA-451