Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer
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Colin Siu-Chi Lam1, Lui Ng1, Ariel Ka-Man Chow1,2, Timothy Ming-Hun Wan1, Simon Yau1, Nathan Shiu-Man Cheng1, Sunny Kit-Man Wong1, Johnny Hon-Wai Man1, Oswens Siu-Hung Lo1, Dominic Chi-Chung Foo1, Jensen Tung-Chung Poon1, Roberta Wen-Chi Pang1,2, Wai-Lun Law1,2
1Division of Colorectal Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
2Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Roberta Wen-Chi Pang, email: [email protected]
Lui Ng, email: [email protected]
Keywords: CRC, liver metastasis, miR-885-5p, EMT, CPEB2
Received: August 16, 2016 Accepted: February 20, 2017 Published: March 02, 2017
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.
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