The Possible Underlying Molecular Mechanism Of Mi R-148a-3p In Drug Resistance Of Gastric Caner

Background:Gastric cancer is the high incidence of malignant tumor worldwide and ranks as the second leading cause in global cancer mortality.Although surgery is the primary treatment for the early stage of gastric caner.The development of multidrug resistance(MDR) in gastric cancer cells is the most primary reason for failed chemotherapy and an important cause for relapse and metastasis of gastric cancer(GC). Therefore, it’s a vital direction in cancer research to clarify the underlying mechanisms of MDR in GC and to search for the drug targets for reversing MDR. Micro RNAs(miRNAs) are a cluster of about 22-nucleotides, non-coding RNA molecules that negatively regulate its target genes expression by binding to the 3 untranslatedregion(3 UTR) of mRNA and resulting in translation inhibition or mRNA degradation.It has been demonstrated that miRNAs may mediate diverse physiological functions, such as cell differentiation, apoptosis, proliferation,and metabolism.And so me studies suggested that some miRNAs modulate drug resistance in some cancers.There has no reports about the role of miR-148a-3p in gastric drug resistance cells,so we try to reveal the function and the underlying molecular mechanism of miR-148a-3p in SGC7901/ADR cel s. Objective: To investigate the function and the underlying molecular mechanism of miR-148a-3p in MDR of gastric cancer cel s. Methods:1. Using qRT-PCR to detect the expression of miR-148a-3p between SGC7901/ADR cel s and its parent cel s SGC7901.2.Up-regulated the expression of miR-148a-3p in SGS7901/ADR and down-regulated miR-148a-3p expression in SGC7901 through transient transfection of miR-148a-3p mimic and inhibitor.Using in vitro MTT drug resistance assay and cell apoptosis assays to analyses the role in gastric cancer drug resistance.3. Explore the underlying molecular mechanism of miR-148a-3p in drug resistance of gastric cancer. Results:1.miR-148a-3p was down-regulated in SGC7901/ADR cells compared to its parent cel s SGC7901.2.Up-regulated the expression of miR-148a-3p sensitized SGC7901/ADR to anticancer drugs and increased susceptibility to drug- induced apoptosis.And down-regulated of miR-148a-3p insensitized SGC7901 to anticancer drugs and decrease drug-induced apoptosis.3.Western-blot and q RT-PCR results revealed that ERBB3 may be one of the target genes of miR-148a-3p.4.Western-blot results showed that the expression of p-Akt was decreased in SGC7901/ADR cells transfected with si- ERBB3 compared to the cells that transfected with si-NC. Conclusion: miR-148a-3p could modulate drug resistance in gastric cancer cel s in part through ERBB3/PI3K/Akt signal pathway.