OncoTargets and Therapy (May 2020)
Metformin Suppresses the Proliferation and Promotes the Apoptosis of Colon Cancer Cells Through Inhibiting the Expression of Long Noncoding RNA-UCA1
Abstract
Jianbo Guo, Yan Li, He Duan, Lu Yuan Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Lu YuanDepartment of General Surgery, The Fourth Affiliated Hospital of China Medical University, 4 Chongshan East Street, Shenyang, Liaoning 110032, People’s Republic of ChinaTel/Fax +86-2462043155Email [email protected]: LncRNA-UCA1 has been proven to facilitate the proliferation and metastasis of colon cancer. Whether metformin inhibits the progression of colon cancer by suppressing lncRNA-UCA1 remains unknown. In this research, we aimed to explore the role of Metformin playing in pathogenesis of colon cancer.Materials and Methods: Using qRT-PCR, we measured the expression of five tumor-promoting lncRNAs in SW480 and SW620 colon cancer cells. Then, we conducted Western blotting and immunohistochemistry to evaluate the effects of MET or UCA1 knockdown or the combined MET+ UCA1 knockdown on the activities of the PI3K/AKT and ERK pathways in vitro and in tumor tissues obtained from tumor-bearing nude mice.Results: The results from CCK-8 assays showed that MET dose-dependently and time-dependently inhibited the viability of the colon cancer cells in vitro. Flow cytometry revealed that MET promoted the apoptosis of the SW480 and SW620 cells. qRT-PCR showed that lncRNA-UCA1 had the highest expression among the five lncRNAs. Suppressing UCA1 expression by siRNA or shRNA could further enhance the metformin-mediated anticancer effects against colon cancer in vitro and in vivo. Metformin decreased the UCA1 expression and further inhibited the proliferation and promoted the apoptosis of the colon cancer cells, which were associated with inactivation of the PI3K/AKT and ERK signaling pathways in vitro and in the tumor tissues obtained from the mice.Conclusion: These results indicated that metformin has potential anticancer properties and revealed the anticancer mechanisms of metformin against colon cancer via regulating lncRNA-UCA1.Keywords: colonic neoplasms, metformin, urothelial cancer associated 1 noncoding RNA
