The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer

Abstract

// Wei-Cheng Liang 1, 2 , Wei-Ming Fu 3 , Cheuk-Wa Wong 1, 2 , Yan Wang 1 , Wei-Mao Wang 1 , Guo-Xin Hu 4 , Li Zhang 1 , Li-Jia Xiao 5 , David Chi-Cheong Wan 1 , Jin-Fang Zhang 1, 6 , Mary Miu-Yee Waye 1, 2 1 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China 2 Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China 3 Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou, P.R. China 4 Department of Infectious Diseases, Peking University Shenzhen Hospital, Shenzhen, P.R. China 5 Department of Clinical Laboratory, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, P.R. China 6 Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China Correspondence to: Mary Miu-Yee Waye, e-mail: mary-waye@cuhk.edu.hk Jin-Fang Zhang, e-mail: zhangjf06@cuhk.edu.hk Keywords: miRNA sponges, lncRNA, ceRNA Received: February 05, 2015 Accepted: May 23, 2015 Published: June 05, 2015 ABSTRACT Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.