Timothy Ming-Hun Wan, Nathan Shiu Man Cheng, Roberta Pang, Colin S.C. Lam, Johnny Hon Wai Man, Oswens Siu-Hung Lo, Ariel K.M. Chow, Sunny Kit Man Wong, Lui Ng, Dominic Chi-Chung Foo, Wai Lun Law, Simon Yau, and Jensen T. C. Poon
// Colin Siu-Chi Lam 1 , Lui Ng 1 , Ariel Ka-Man Chow 1, 2 , Timothy Ming-Hun Wan 1 , Simon Yau 1 , Nathan Shiu-Man Cheng 1 , Sunny Kit-Man Wong 1 , Johnny Hon-Wai Man 1 , Oswens Siu-Hung Lo 1 , Dominic Chi-Chung Foo 1 , Jensen Tung-Chung Poon 1 , Roberta Wen-Chi Pang 1, 2 , Wai-Lun Law 1, 2 1 Division of Colorectal Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 2 Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Correspondence to: Roberta Wen-Chi Pang, email: robertap@hku.hk Lui Ng, email: luing@hku.hk Keywords: CRC, liver metastasis, miR-885-5p, EMT, CPEB2 Received: August 16, 2016 Accepted: February 20, 2017 Published: March 02, 2017 ABSTRACT 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.