Carcinogenesis, 2016, Vol. 37, No. 9, 858–869 doi:10.1093/carcin/bgw079 Advance Access publication August 4, 2016 Original Manuscript
0riginal manuscript
miR-200b induces cell cycle arrest and represses cell growth in esophageal squamous cell carcinoma Hai-Feng Zhang1,2,3, Abdulraheem Alshareef2, Chengsheng Wu2, Ji-Wei Jiao1,4, Poul H.Sorensen3, Raymond Lai2, Li-Yan Xu4 and En-Min Li1,* The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong 515041, China, 2Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada, 3Department of Molecular Oncology, British Columbia Cancer Research Centre and Department of Pathology, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada and 4Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong 515041, China 1
*To whom correspondence should be addressed. Tel: +86 754 88900464; Fax: +86 754 88900847; Email: [email protected] Correspondence may also be addressed to Li-Yan Xu. Tel: +86 754 88900413; Fax: +86 754 88900847; Email: [email protected]
Abstract miR-200b is a pleiotropically acting microRNA in cancer progression, representing an attractive therapeutic target. We previously identified miR-200b as an invasiveness repressor in esophageal squamous cell carcinoma (ESCC), whereas further understanding is warranted to establish it as a therapeutic target. Here, we show that miR-200b mitigates ESCC cell growth by inducing G2-phase cell cycle arrest and apoptosis. The expression/activation of multiple key cell cycle regulators such as CDK1, CDK2, CDK4 and Cyclin B, and the Wnt/β-Catenin signaling are modulated by miR-200b. We identified CDK2 and PAF (PCNA-associated factor), two important tumor-promoting factors, as direct miR-200b targets in ESCC. Correlating with the frequent loss of miR-200b in ESCC, both CDK2 and PAF levels are significantly increased in ESCC tumors compared to case-matched normal tissues (n = 119, both P
0riginal manuscript
miR-200b induces cell cycle arrest and represses cell growth in esophageal squamous cell carcinoma Hai-Feng Zhang1,2,3, Abdulraheem Alshareef2, Chengsheng Wu2, Ji-Wei Jiao1,4, Poul H.Sorensen3, Raymond Lai2, Li-Yan Xu4 and En-Min Li1,* The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong 515041, China, 2Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada, 3Department of Molecular Oncology, British Columbia Cancer Research Centre and Department of Pathology, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada and 4Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong 515041, China 1
*To whom correspondence should be addressed. Tel: +86 754 88900464; Fax: +86 754 88900847; Email: [email protected] Correspondence may also be addressed to Li-Yan Xu. Tel: +86 754 88900413; Fax: +86 754 88900847; Email: [email protected]
Abstract miR-200b is a pleiotropically acting microRNA in cancer progression, representing an attractive therapeutic target. We previously identified miR-200b as an invasiveness repressor in esophageal squamous cell carcinoma (ESCC), whereas further understanding is warranted to establish it as a therapeutic target. Here, we show that miR-200b mitigates ESCC cell growth by inducing G2-phase cell cycle arrest and apoptosis. The expression/activation of multiple key cell cycle regulators such as CDK1, CDK2, CDK4 and Cyclin B, and the Wnt/β-Catenin signaling are modulated by miR-200b. We identified CDK2 and PAF (PCNA-associated factor), two important tumor-promoting factors, as direct miR-200b targets in ESCC. Correlating with the frequent loss of miR-200b in ESCC, both CDK2 and PAF levels are significantly increased in ESCC tumors compared to case-matched normal tissues (n = 119, both P
