miR-30b-5p targets CD73 and inhibits gastric cancer migration and invasion via PTEN/AKT/GSK3β/mTOR pathway

Abstract

Abstract Background and purpose: Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. CD73 has been found to be overexpressed in a variety of cancers including GC and is associated with poor cancer prognosis. However, its specific mechanisms regulating the progression of GC are not sufficiently clear. In this study, we aimed to investigate the function of CD73 in GC and to explore its upstream and downstream molecular mechanisms. Methods: Immunohistochemistry (IHC) and western blotting were used to detect the protein levels of CD73 and other proteins. Quantitative real-time PCR (RT-qPCR) was used to detect the RNA levels of CD73, miR-30b-5p, and other genes. CCK-8 and clonogenic assays were used to test cell proliferation. Scracth and Transwell were used to analyze the migration and invasion of GC cells. In addition, CD73 stable knockdown and overexpression cell lines were established to detect the expression of PTEN/AKT/GSK3β/mTOR pathway-related molecules. Dual luciferase reporter assay was used to detect the binding of CD73 and miR-30b-5p. Results: We found that miR-30b-5p targeted binding and inhibited CD73 overexpression, and suppressed GC cell proliferation, migration and invasion in GC cells. We further revealed that these effects were mediated through the PTEN/AKT/GSK3β/mTOR signalling pathway. Conclusions: In summary, our results reveal the relevance of the miR-30b-5p/CD73/PTEN/AKT/GSK3β /mTOR regulatory axis to migration and invasion in gastric cancer.