OncoTargets and Therapy (Feb 2021)
MicroRNA-1249 Targets G Protein Subunit Alpha 11 and Facilitates Gastric Cancer Cell Proliferation, Motility and Represses Cell Apoptosis
Abstract
Hongzhu Zhang,1,* Tingting Fu,1,* Cuiping Zhang2 1Department of Gastroenterology, Jinan Jigang Hospital, Jinan, Shandong, 250101, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cuiping ZhangDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266000, People’s Republic of ChinaEmail [email protected]: The purpose of our study was to investigate the effects of miR-1249 in gastric cancer.Methods: By analyzing the data obtained from TCGA database, the expression and prognosis of miR-1249 in gastric cancer patients were analyzed. Then, CCK8, colony forming and transwell assays were used to test cell proliferation and motility. The cell apoptosis was detected by flow cytometry. The Pearson correlation coefficient analyzed was applied to analyze the correlation between GNA11 and miR-1249. qRT-PCR and Western blotting assays were employed to detect the mRNA and protein levels.Results: We discovered that miR-1249 was highly expressed and was associated with a worse prognosis in gastric cancer patients. Besides, miR-1249 was up-regulated in gastric cancer cell lines (AGS, MKN45 and SNU1). More interestingly, miR-1249 exerted facilitating impacts on gastric cancer cell proliferation and motility, whereas miR-1249 acted as a suppressing effect on gastric cancer apoptosis. G protein subunit alpha 11 (GNA11) was a target gene of miR-1249 and was negatively correlated with miR-1249. Furthermore, GNA11 was negatively regulated by miR-1249. Additionally, GNA11 was lowly expressed in gastric cancer tissues and cell lines, as well as low GNA11 expression, was related to poor overall survival results in gastric cancer patients. The promoting influences of miR-1249 over-expression on AGS cell proliferation and motility was rescued by GNA11 over-expression, which might be achieved by regulating PI3K/AKT/mTOR signalling pathway.Conclusion: Above all, we concluded that miR-1249 was concerned with the progression of gastric cancer through regulating GNA11, suggesting that miR-1249 and GNA11 might serve as predictive biomarkers for gastric cancer therapy.Keywords: gastric cancer, miR-1249 mimic/inhibitor, G protein subunit alpha 11, target, proliferation, apoptosis, PI3K/AKT/mTOR pathway
