Analysis And Prediction Research Of MicroRNAs Chip In Drug-resistant Small Cell Lung Cancer

Purpose: Small cell lung cancer (SCLC) accounted for about15%of all lung cancerwith rapid growth, early metastasis and high recurrence as characteristics.In recentyears, the incidence of SCLC was increasing. Chemotherapy is the main treatment ofSCLC.The majority patients of SCLC is very sensitive for first-line treatment, but hasa high rate of recurrence. Drug resistance is the key point of relapse.The efficiencyafter second-line chemotherapy of relapsed SCLC patients depends mainly onremission. Patients in remission period shorter than3months has high resistance tofirst-line chemotherapy regimen. MicroRNA (miRNA) are a family of non-coding19-to25-nucleotide RNA duplexes that post-transcriptionally regulate gene expression bybinding specific mRNA or regulate protein translation process of specific mRNA.miRNAs function in the regulation of a range of bioprocess including cell growth,differentiation, proliferation and apoptosis, hormone secretion and tumor formation.Recent studies show that miRNAs could have intimate relationship with drugresistance of cancer. In our study,through detecting the expression of miRNA inpatients according to remission, screening differentially expressed miRNA and predictthe target gene to explore the biological mechanism of drug-resistance afterchemotherapy of SCLC, find the potential targets for therapeutic intervention.Theopportunity to control the recurrence, improve the survival and eventually change thecurrent treatment of SCLC will be raised.Methods: Between January2011and December2012,a total of30patients serum withSCLC,who did not received surgery and adjuvant chemotherapy in PLA medicalschool were included in the studies. The patients were divided into3groups accordingto the different remission: group A (remission≤3months), group B (3months <remission <6months), group C (remission≥6months). Phalanx miRNA OneArrayTMwere used to find out differentially expressed miRNAs. The significantly differentially expressed miRNA were testified by real-time quantitative PCR. TargetScanHuman andPictar online softwares was used to predict the potential target genes of these miRNAs.Results: Comparing with the group C, chips screened out that5miRNAs increasedand1miRNAs decreased more than2-fold in group A.13miRNAs increased morethan2-fold in group B.The real-time quantitative PCR validation results wereconsistent with the chip screening, which showed miR-4728-3p、miR-4443、miR-1825significantly differentially expressed. The result of TargetScanHuman5.1and PicTarpredicted target genes of miRNA. The enriched pathways of target genes werepredicted by KEGG, including PI3K-AKT signaling pathway and P53signalingpathway, all of which involved in cell proliferation, differentiation, and apoptosis ofSCLC. The KEGG also showed ITGA3and IKBKB、RXRB as the target genes ofmiR-1825were distributed in PI3K-AKT and P53signaling pathway respectively,RAR-β、AKT1as the target genes of miR-4443were distributed in PI3K-AKT andP53signaling pathway respectively.Conclusion: We established the screening of miRNA associated with drug-resistancein SCLC. The enriched function about target genes of miRNA were predicted.PI3K-AKT and P53signaling pathway are closely related with formation anddevelopment of SCLC. ITGA3、IKBKB and RXRB as the targets of miR-1825, RAR-β、AKT1as the target genes of miR-4443were distributed in two signaling pathwaysrespectively.We have suspected that these genes plays an important role indrug-resistance of SCLC after chemotherapy.