Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer

• Published in: Oncotarget Vol. 8; no. 16; pp. 26858 - 26870
• Main Authors: Lam, Colin Siu-Chi, Ng, Lui, Chow, Ariel Ka-Man, Wan, Timothy Ming-Hun, Yau, Simon, Cheng, Nathan Shiu-Man, Wong, Sunny Kit-Man, Man, Johnny Hon-Wai, Lo, Oswens Siu-Hung, Foo, Dominic Chi-Chung, Poon, Jensen Tung-Chung, Pang, Roberta Wen-Chi, Law, Wai-Lun
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 18.04.2017
• Subjects: 3' Untranslated Regions; Animals; Cell Line, Tumor; Cell Movement - genetics; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Cytoskeleton - metabolism; Disease Models, Animal; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Liver Neoplasms - secondary; Male; Mice; MicroRNAs - genetics; Neoplasm Metastasis; Neoplasm Staging; Research Paper; RNA Interference; RNA-Binding Proteins - genetics; liver metastasis; CRC; CPEB2; EMT; miR-885-5p
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15844

Colorectal cancer is the third most common cancer in the world and liver is the most frequent site of distant metastasis with poor prognosis. The aim of this study is to investigate microRNAs leading to liver metastasis. We applied microarray analysis and quantitative PCR to identify and validate dysregulated miRNAs in liver metastases when compared to primary CRCs. Functional significance and the underlying molecular mechanism of selected miRNA was demonstrated by a series of in vitro and in vivo assays. Our microarray analysis and subsequent quantitative PCR validation revealed that miR-885-5p was strongly up-regulated in liver metastases and in CRC cell-lines derived from distant metastases. Overexpression of miR-885-5p significantly induced cell migration, cell invasion, formation of stress fibre in vitro and development of liver and lung metastases in vivo. MiR-885-5p induced metastatic potential of CRC by repressing cytoplasmic polyadenylation element binding protein 2 transcription through directly binding to two binding sites on its 3' untranslated region, and consequently led to up-regulation of TWIST1 and hence epithelial-mesenchymal transition. Our findings demonstrated the overexpression of miR-885-5p in liver metastasis and its roles in inducing CRC metastasis, potentiating development of miR-885-5p inhibitor to treat advanced CRC in the future.