Cancer Management and Research (Dec 2019)
miR-194 Inhibits the Proliferation of SW620 Colon Cancer Stem Cells Through Downregulation of SSH2 Expression
Abstract
Bo Sun,1,* Yan-Tian Fang,1,* Dan-Juan Jin,2 Zong-You Chen,3 Zhen-Yang Li,3 Xiao-Dong Gu,3 Jian-Bin Xiang3 1Department of Gastric Cancer, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of General Surgery, Songjiang District Central Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Dong Gu; Jian-Bin XiangDepartment of General Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, People’s Republic of ChinaTel +86-21-5288 7044; +86-21-5288 7040Fax +86-21-62495490Email [email protected]; [email protected]: Colorectal cancer (CRC) stem cells are tumorigenic, capable of self-renewal, and resistant to therapy. Although the expression pattern and functions of micro RNA (miR)-194 in CRC cells have been widely investigated, little is known about its role in CRC stem cells. Therefore, the aim of this study was to investigate the potential role of miR-194 in CRC stem cells.Materials and methods: CRC stem cells were isolated from the SW620 colon cancer cell line using microbeads. The expression levels of miR-194 and slingshot 2 (SSH2) in CRC stem cells were detected by RT-PCR and Western blot. A luciferase reporter assay was performed to confirm that miR-194 directly targets SSH2. Proliferation of CRC stem cells was examined by colony formation and MTT assays. Apoptosis in CRC stem cells was detected by cell cycle and apoptosis assays. The role of miR-194 in tumor growth was determined in vivo.Results: Cells positive for CD44 and CD133 accounted for approximately 88.7% of the isolated population after microbead isolation. We reveal for the first time that miR-194 expression is decreased in CRC stem cells. Specifically, miR-194 is involved in inhibiting the proliferation of CRC stem cells and promoting CRC stem cell apoptosis by directly targeting SSH2. Furthermore, overexpression of miR-194 resulted in blocking the G1/S transition, the induction of cellular apoptotic process, thereby suppressing the malignant behaviors of CRC stem cells.Conclusion: This study represents a novel characterization of miR-194 function in CRC stem cells, which may aid in the development of promising therapeutic strategies targeting CRC.Keywords: colorectal cancer, miR-194, SSH2, proliferation, stem cell
