MicroRNA-199a-5p suppresses the cell growth of colorectal cancer by targeting oncogene Caprin1
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ORIGINAL ARTICLE
MicroRNA‑199a‑5p suppresses the cell growth of colorectal cancer by targeting oncogene Caprin1 Xiangyang Yu1 · Yanfang He2 · Yan Wang2 · Yajuan Tang2 · Yanjuan Guo2 · Jinling Yuan2 · Jinghe Bai2 · Tao Yao2 · Xiongzhi Wu1 Received: 3 June 2020 / Accepted: 8 September 2020 © King Abdulaziz City for Science and Technology 2020
Abstract MicroRNAs-199a-5p (miR-199a-5p) plays critical regulatory roles in various types of human cancers. However, the biological function and regulatory mechanisms of miR-199a-5p in colorectal cancer (CRC) remain unclear. The aim of this study was to investigate the role of miR-199a-5p in CRC and possible mechanisms of its action. The expression of miR-199a-5p in CRC tumor tissues was validated using quantitative real-time PCR (qRT-PCR). The effects of miR-199a-5p on cell proliferation and apoptosis were evaluated in vitro. Then, the association of miR-199a-5p and its downstream target was investigated in both cell line and clinical specimens. Furthermore, gain- and loss-of-function studies of cytoplasmic activation/ proliferation-associated protein-1 (Caprin1) were performed to assess whether the suppressive effect of on CRC cells were via targeting Caprin1. Using a microarray platform, we focused on miR-199a-5p for further research, which was one of the most markedly downregulated miRNAs in CRC tumor tissues. Functionally, the overexpression of miR-199a-5p inhibited proliferation and induced apoptosis in both HTC116 and SW480 cells. Furthermore, cytoplasmic activation/proliferationassociated protein-1 (Caprin1), a well-known oncogene, was directly targeted by miR-199a-5p. It was also observed that Caprin1 was upregulated, and inversely correlated with miR-199a-5p levels in CRC tissues. Further investigations revealed that knockdown of Caprin1 by siRNA has similar role with miR-199a-5p overexpression in CRC cells, suggesting the oncogenic role of Caprin1 in CRC. In the contrast, we found that overexpression of Caprin1 reversed the suppressive effects of miR-199a-5p on CRC cells. Collectively, our study suggests that miR-199a-5p/Caprin1 axis may serve as potential therapeutic targets for the treatment of CRC. Keywords MicroRNA-199a-5p · Tumor suppressor · Colorectal cancer · Proliferation · Apoptosis · Caprin1
Introduction Colorectal cancer (CRC) is one of the most prevalent malignancies and the leading causes of cancer mortality worldwide (Gaedcke et al. 2012; Siegel et al. 2016). Recently, the morbidity of CRC has been increasing in Asian countries, * Xiongzhi Wu [email protected] 1
Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, No.22 Qi‑Xiang‑Tai Road, Tianjin 300000, People’s Republic of China
Department of Obstetrics and Gynecology, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, People’s Republic of China
2
including China, Singapore, Korea and Japan, due to d
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