Research On MiRNA Related With Cisplatin-based Chemotherapy Response In Non-small Cell Lung Cancer

Objective：Lung cancer is the most widespread cancer and the leading cause ofcancer-related death in the world. It is still a significant impediment that cancer cellsbecome resistant to chemotherapeutic agents during treatment. The molecularmechanisms of lung cancer cell resistance to chemotherapeutics are very complexinvolving multiple paths, and the mechanisms are poorly understood. MicroRNAs(miRNAs) are a class of small, single-stranded, non-coding RNA. MiRNAs regulategene expression at the post-transcriptional level, and they play important roles in crucialbiological processes including development, differentiation, proliferation, apoptosis andtumorigenesis. Recently, many researches found that miRNAs could also affectplatinum resistance in cancer cells by regulating the biological processes. The newstudy suggests that circulating miRNA may become useful biomarkers forchemotherapy response in cancer patients. The aim of this study was to explore therelationship between plasma miRNA expression and chemotherapeutic responsethrough measuring the levels of plasma miRNAs in advanced NSCLC patients whoreceive cisplatin-based chemotherapy and to investigate the potential of miRNAs asbiomarkers to predict the response to chemotherapy.Methods:(1) We measured the plasma levels of16miRNAs by real-time quantitativeRT-PCR in96patients to selecte difference miRNAs between lung cancer parents andhealthy controls.(2) We used RT-PCR to conpare the expression of plasma miRNAs ofresponsers and non-responsers according to chemotherapy. We also survey the levels ofmiRNAs after2cycles of chemotherapy.(3) We make overexpression of candidatemiRNA in A549/CDDP to test the effect to the drug sensitivity.Results（:1）The results of rt-PCR showed the expression levels of miR-10a、miR-125b、miR-126、miR-15b、miR-152、miR-22、miR-221and miR-29b in NSCLC patientsplasma compared with healthy controls were statistically significant.(2) The results of rt-PCR showed the expression levels of miR-10a、miR-125b、miR-126、miR-130a、miR-152、miR-22、miR-221and miR-29b in responsers compared with non-responserswere statistically significant,and levels of the8miRNAs can change with chemotherapyresponse. The ROC curve area of miR-125b is the biggest (AUC=0.7389).(3)Overexpression of miR-125b in A549/DDP could enhance cell cisplatin sensitivitysignificant.Conclusions: The expression levels of miR-10a、miR-125b、miR-126、miR-15b、miR-152、miR-22、miR-221and miR-29b in plasma could be potential diagnosticbiomarkers for NSCLC according to the relevance. The expression levels of plasmamiR-10a、miR-125b、miR-126、miR-130a、miR-152、miR-22、miR-221and miR-29bin NSCLC patients may be used as biomarkers to predict cisplatin-based chemotherapyresponse and survy the therapeutic effect. The finding that overexpression of miR-125bin A549/DDP can enhance cell cisplatin sensitivity significant gives new breakthoughtfor overcoming chemotherapeutic resistance in NSCLC and develop new targetedtherapeutics.