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Role and mechanism of miR-222 in arsenic-transformed cells for inducing tumor growth

2016; Impact Journals LLC; Volume: 7; Issue: 14 Linguagem: Inglês

10.18632/oncotarget.7525

1949-2553

Min Wang, Xin Ge, Jitai Zheng, Dongmei Li, Xue Liu, Lin Wang, Chengfei Jiang, Zhumei Shi, Lianju Qin, Jiayin Liu, Hushan Yang, Liu L, Jun He, Linlin Zhen, Bing‐Hua Jiang,

RNA regulation and disease

// Min Wang 1 , Xin Ge 1, * , Jitai Zheng 1, * , Dongmei Li 1, 4 , Xue Liu 1 , Lin Wang 1, 4 , Chengfei Jiang 1 , Zhumei Shi 1 , Lianju Qin 3 , Jiayin Liu 3 , Hushan Yang 5 , Ling-Zhi Liu 6 , Jun He 6 , Linlin Zhen 2 , Bing-Hua Jiang 1, 6 1 State Key Laboratory of Reproductive Medicine, Department of Pathology, and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China 2 Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu, China 3 Center of Clinical Reproductive Medicine, Jiangsu Province Hospital, Nanjing, Jiangsu, China 4 Ninggao Personalized Medicine and Technology Innovation Center, Nanjing, Jiangsu, China 5 Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA 6 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA * These authors contributed equally to this work Correspondence to: Bing-Hua Jiang, e-mail: binghjiang@yahoo.com and bhjiang@njmu.edu.cn Linlin Zhen, e-mail: simu1027@sina.com Keywords: BEAS-2B cells, miR-222, PTEN, ARID1A, tumor growth Received: September 26, 2015 Accepted: January 14, 2016 Published: February 20, 2016 ABSTRACT High levels of arsenic in drinking water, soil, and air are associated with the higher incidences of several kinds of cancers worldwide, but the mechanism is yet to be fully discovered. Recently, a number of evidences show that dysregulation of microRNAs (miRNAs) induces carcinogenesis. In this study, we found miR-222 was upregulated in arsenic-transformed human lung epithelial BEAS-2B cells (As-T cells). Anti-miR-222 inhibitor treatment decreased cell proliferation, migration, tube formation, and induced apoptosis. In addition, anti-miR-222 inhibitor expression decreased tumor growth in vivo . We also found that inhibition of miR-222 induced the expression of its direct targets ARID1A and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and activated apoptosis of As-T cells in part through ARID1A downregulation. These results indicate that miR-222 plays an important role in arsenic-induced tumor growth.