OncoTargets and Therapy (Apr 2021)
MiR-140-3p Impedes Gastric Cancer Progression and Metastasis by Regulating BCL2/BECN1-Mediated Autophagy
Abstract
Jianliang Chen,1,2,* Shengqiang Cai,1,2,* Tianchun Gu,1,2 Fei Song,1,2 Yingchun Xue,1,2 Di Sun1,2 1Department of General Surgery, People’s Hospital of Jingjiang, Taizhou, 214500, Jiangsu, People’s Republic of China; 2Seventh Clinical Medical College of Yangzhou University, Taizhou, 214500, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di SunDepartment of General Surgery, People’s Hospital of Jingjiang, 28 Zhongzhou Road, Jingjiang, Taizhou, 214500, Jiangsu, People’s Republic of ChinaTel +86-18052633030Email [email protected]: MiRNAs have been proven to modulate the progression of gastric cancer (GC). In this field, we evaluated the role and mechanism of miR-140-3p in GC.Methods: Western blotting and qRT-PCR were used to detect the levels of miR-140-3p and BCL2. The interaction of miR-140-3p and BCL2 was confirmed by dual-luciferase reporter and miRNA pull-down assays. CCK-8, EdU, wound healing, and Transwell invasion assays were performed to evaluate cell proliferation, migration and invasion. Autophagy was analyzed using Western blot analysis of the LC3-II/I ratio and immunofluorescence staining. A xenograft model was established to reveal the role of miR-140-3p in tumorigenesis.Results: In GC cell lines and tissues, miR-140-3p was highly expressed, and BCL2 was expressed at low levels. MiR-140-3p directly inhibited BCL2 expression and indirectly promoted BECN1 expression, and BCL2 inhibited BECN1 expression. MiR-140-3p overexpression or silencing restrained or facilitated migration, invasion and EMT in GC cells. Moreover, we noticed that overexpression or downregulation of miR-140-3p promoted or suppressed BECN1-dependent autophagy in GC cells. BCL2 introduction or BECN1 silencing in GC cells partially blocked the effects of miR-140-3p. In conclusion, miR-140-3p directly downregulated the expression of BCL2, BCL2 downregulation further activated BECN1-dependent autophagy, and autophagy activation further inhibited EMT.Conclusion: miR-140-3p may act as a tumor suppressor by targeting BCL2 and regulating downstream BECN1-induced autophagy and metastasis in GC progression.Keywords: miR-140-3p, gastric cancer, BCL2, BECN1, autophagy, EMT
