MiR-133a-3p Enhances Chemosensitivity Of Cisplatin To Non-small Cell Lung Cancer By Targeting RFC3

Chemoresistance has become a primary hurdle in the therapeutic effect of non-small cell lung cancer(NSCLC).Emerging evidences have demonstrated that micro RNAs(miRNAs)are closely associated with the chemoresistance of NSCLC.The rapid development and high lethality of malignant tumors are closely related to its following characteristics: unlimited replication and proliferation,continuous angiogenesis,avoiding cell death(apoptosis),infiltration and metastasis of tissues,continuous autonomous growth,signal generation,insensitivity to growth inhibitory signals,high energy output,immune escape,genome instability,etc.In recent years,studies on miRNAs have found that miRNAs participate in important processes such as tumor proliferation,apoptosis,and angiogenesis through negative regulation of target genes,and mediate the occurrence and development of tumors.As a common tumor-related miRNA,miR-133a-3p is low-expressed in many cancers,and plays a role in inhibiting tumors,and can prevent the development of breast cancer,gastric cancer,pancreatic cancer and other cancers.Studies have shown that overexpression of miR-133 a significantly increases the sensitivity of A549/DDP cells to DDP.Our investigation aims to explore the possible effects and investigate the underlying mechanisms of miR-133a-3p on NSCLC resistance to cisplatin(DDP)treatment.In the present study,miR-133a-3p was obviously down-regulated in DDP-resistant cells(A549/DDP and SPC-1/DPP)by q RT-PCR assay.In addition,up-regulation of miR-133a-3p notably inhibited cell proliferation,promoted cell apoptosis and induced cell cycle arrest of DDP-resistant NSCLC cells,and enhanced the sensitivity of DDP in DDP-resistant NSCLC cells by CCK-8,flow cytometry,and western blot analysis.Mechanically,Replication factor C(RFC)3 was proven as a specific downstream of miR-133a-3p and negatively associated with miR-133a-3p.Furthermore,over-expression of RFC3 partially restored the effects of miR-133a-3p mimic on cell proliferation,cell apoptosis,cell cycle arrest,and the sensitivity of DDP in DDP-resistant NSCLC cells.This study provides an experimental basis that miR-133a-3p may act as a novel diagnostic target in NSCLC resistance to DDP treatment.