miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression

// Ya-Ping Ye 1, 2, 3, * , Ping Wu 1, 2, 3, * , Chun-cai Gu 1, 2, 3, * , Dan-ling Deng 1, 2, 3 , Hong-Li Jiao 1, 2, 3, Ting-Ting Li 1, 2, 3 , Shu-Yang Wang 1, 2, 3 , Yong-Xia Wang 1, 2, 3 , Zhi-Yuan Xiao 1, 2, 3 , Wen-ting Wei 1, 2, 3 , Yan-Ru Chen 1, 2, 3 , Jun-Feng Qiu 1, 2, 3 , Run-Wei Yang 1, 2, 3 , Jie Lin 1, 2, 3 , Li Liang 1, 2, 3 , Wen-Ting Liao 1, 2, 3 , Yan-Qing Ding 1, 2, 3 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 3 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Wen-Ting Liao, email: liaowt2002@gmail.com Yan-Qing Ding, email: dyq@fimmu.com Keywords: miR-450b-5p, Wnt/β-Catenin pathway, colorectal cancer, progression, KRAS Received: May 13, 2016 Accepted: July 14, 2016 Published: August 2, 2016 ABSTRACT The development and progression of CRC are regarded as a complicated network and progressive event including genetic and/or epigenetic alterations. Recent researches revealed that MicroRNAs are biomarkers and regulators of CRC progression. Analyses of published microarray datasets revealed that miR-450b-5p was highly up-regulated in CRC tissues. In addition, high expression of miR-450b-5p was significantly associated with KRAS mutation. However, the role of miR-450b-5p in the progression of CRC remains unknown. Here, we sought to validate the expression of miR-450b-5p in CRC tissues and investigate the role and underlying mechanism of miR-450b-5p in the progression of CRC. The results revealed that miR-450b-5p was up-regulated in CRC tissues, high expression level of miR-450b-5p was positively associated with poor differentiation, advanced TNM classification and poor prognosis. Moreover, miR-450b-5p was especially high in KRAS-mutated cell lines and could be up-regulated by KRAS/AP-1 signaling. Functional validation revealed that overexpression of miR-450b-5p promoted cell proliferation and tumor growth while inhibited apoptosis of CRC cells. Furthermore, we demonstrated that miR-450b-5p directly bound the 3’-UTRs of SFRP2 and SIAH1, and activated Wnt/β-Catenin signaling. In conclusion, miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression. Collectively, our work helped to understand the precise role of miR-450b-5p in the progression of CRC, and might promote the development of new therapeutic strategies against CRC.