MiR-513a-3p Regulates Chemosensitivity Of Lung Adenocarcinoma Cells By Targeting GSTP1

Lung cancer owns the leading mortality from malignant tumors in humanbeings. Systemic therapy remains the main treatment strategy for advanced stagenon small cell lung cancers (NSCLC). Combinational chemotherapy with aplatinum-based regimen has emerged as standard therapy for patients withadvanced stage NSCLC. However, cisplatin resistance is a challenge againstsuccessful clinical use. It is reported that90%of caner patients died from drugresistance. Many factors, including genes and proteins, contribute to cisplatinresistance. Among theses, GSTP1gene affects cisplatin resistance significantly. Incells, GSTP1gene is regulated by a network of factors, among which microRNA(miRNA) has been given wide attention to. MiRNAs are short non-coding RNAmolecules which commonly exist in plant and animal cells. Mature microRNAsare able to modulate gene expression via direct or indirect interaction with mRNAtargets by binding to its3′-UTR. It’s believed that miRNAs modulate thousands ofgenes, one third of all human being genes. So miRNAs play a crucial role in theregulating network of genes, and impose greatly on cellular development anddifferentiation, formulation of tissues, development of cancers and drug resistancein chemotherapy.In this study, we use human lung adenocarcinoma cells A549, A549/CDDPand SPC-A-1as studying models and focus on GSTP1gene, aiming to determinewhether deregulated miRNAs can sensitize human lung adenocarcinoma cells tocisplatin by targeting GSTP1. First we used real-time RT-PCR revealed thatcompared with the parental A549cells, GSTP1mRNA expression was2.7±0.38folds (p<0.05) upregulated in A549/CDDP cells, and the protein level was alsoupregulated significantly, which conformed to the other reports, whilemiR-513a-3p expression was0.34±0.03folds (p<0.05) downregulated in A549/CDDP cells, just parallel changes to the GSTP1. Luciferase activity assayproved that GSTP1was a target gene of miR-513a-3p. Western Blot analysisshowed that after over-expression of miR-513a-3p in A549/CDDP or SPC-A-1cells, GSTP1protein levels decreased. Furthermore, CCK-8assay showed thatoverexpression of miR-513a-3p could enhance cisplatin-induced apoptosis inhuman lung adenocarcinoma cell lines, A549/CDDP and SPC-A-1, by34.5%(p<0.05) and30.8%(p<0.05) respectively. In conclusion, our data demonstratedthat miR-513a-3p could sensitize human lung adenocarcinoma cells to cisplatin bytargeting GSTP1.