Yaoyao Li1, Jijun Wang2, Xiaorong Dai3, Zhengbin Zhou3, Jing Liu3, Yu Zhang2, Yan Li2, Yaying Hou2, Lei Pang2, Xiaohong Wang2, Chenhai Wang2, Zhenfeng Hao3, Yanqing Zhang2, Jixin Jiang4, Hongwei Cheng3, Duonan Yu5. 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.
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 humancolorectal 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. Humancolon 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 humancolon 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.
Authors: Yohei Shimono; Maider Zabala; Robert W Cho; Neethan Lobo; Piero Dalerba; Dalong Qian; Maximilian Diehn; Huiping Liu; Sarita P Panula; Eric Chiao; Frederick M Dirbas; George Somlo; Renee A Reijo Pera; Kaiqin Lao; Michael F Clarke Journal: Cell Date: 2009-08-07 Impact factor: 41.582
Authors: Nerea Bitarte; Eva Bandres; Valentina Boni; Ruth Zarate; Javier Rodriguez; Marisol Gonzalez-Huarriz; Ines Lopez; Jesus Javier Sola; Marta M Alonso; Puri Fortes; Jesus Garcia-Foncillas Journal: Stem Cells Date: 2011-11 Impact factor: 6.277
Authors: Michael M Vickers; Jair Bar; Ivan Gorn-Hondermann; Nirit Yarom; Manijeh Daneshmand; Jennifer E L Hanson; Christina L Addison; Timothy R Asmis; Derek J Jonker; Jean Maroun; Ian A J Lorimer; Glenwood D Goss; Jim Dimitroulakos Journal: Clin Exp Metastasis Date: 2011-11-26 Impact factor: 5.150
Authors: Jakub Godlewski; Michal O Nowicki; Agnieszka Bronisz; Gerard Nuovo; Jeff Palatini; Michael De Lay; James Van Brocklyn; Michael C Ostrowski; E Antonio Chiocca; Sean E Lawler Journal: Mol Cell Date: 2010-03-12 Impact factor: 17.970
Authors: Aaron J Schetter; Suet Yi Leung; Jane J Sohn; Krista A Zanetti; Elise D Bowman; Nozomu Yanaihara; Siu Tsan Yuen; Tsun Leung Chan; Dora L W Kwong; Gordon K H Au; Chang-Gong Liu; George A Calin; Carlo M Croce; Curtis C Harris Journal: JAMA Date: 2008-01-30 Impact factor: 56.272