Long intergenic non-protein coding RNA 00657/miR-218-2-3p/cyclin D1 axis drives gastric cancer chemoresistance

BACKGROUNDMultidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer, which is one of the most common gastrointestinal malignancies, with high morbidity and mortality, leading to an unsatisfactory clinical outcome in patients because gastric cancer cells are more resistant than others to chemotherapeutic drugs. AIMTo explore the impacts of miR-218-2-3p on chemoresistance and the underlying molecular mechanisms in gastric cancer.METHODS miR-218-2-3p expression was verified in gastric cancer tissues of 150 patients by quantitative reverse transcription polymerase chain reaction.miR-218-2-3p was overexpressed in the lentiviral packaging system to demonstrate its functional importance.The molecular mechanism was elucidated through target gene online databases and the miRBase website, dual luciferase reporter assay, western blotting and rescue experiments.RESULTS miR-218-2-3p was expressed at a low level in gastric cancer tissues and MDR cell lines.Low miR-218-2-3p expression was associated with poor prognosis, poor tumor node metastasis stage, and lymph node metastasis in gastric cancer patients.Functionally, overexpression of miR-218-2-3p increased the sensitivity of tumor cells to chemotherapeutic drugs and inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration.In vivo experiments demonstrated that overexpression of miR-218-2-3p significantly inhibited tumor growth and metastasis.According to online databases, long intergenic non-protein coding RNA 00657 (LINC00657) could act as a competing endogenous RNA for miR-218-2-3p to 5 / 48 regulate cyclin D1.The LINC00657/miR-218-2-3p/cyclin D1 axis promoted cell proliferation, inhibited cell apoptosis, promoted cell migration, and increased resistance to chemotherapeutic drugs. CONCLUSIONThe LINC00657/miR-218-2-3p/cyclin D1 axis activating the phosphatidylinositol 3kinase/protein kinase B/mammalian target of rapamycin signaling pathway promoted gastric cancer MDR, while overexpression of miR-218-2-3p reversed gastric cancer MDR.