Identifying Long Non-coding RNA Of Prostate Cancer Associated With Radiosensitivity By Comprehensive Bioinformatics Analysis

Background Long non-coding RNAs(lncRNAs)are a group of RNAs longer than 200 nucleotides,which have many structural features of the m RNAs.Current studies indicate that lncRNAs are involved in proliferation,apoptosis,migration,and metastasis.Increasing evidence has revealed that lncRNAs are implicated in prostate cancer(PCa)radioresistance,metastatic progression,and prognosis.However,most previous studies focused on a single lncRNA based on a small sample size,lacking a large sample with high-throughput transcriptome sequencing data to explore the correlation between lncRNA and radiosensitivity of PCa.This project will use bioinformatics to find effective lncRNAs to predict the radiosensitivity of PCa patients by using large sample and high-throughput transcriptome sequencing data.The aim is to find appropriate biomarkers to evaluate the efficacy of radiotherapy for PCa and to provide new strategies for individualized treatment of patients.Objective Using bioinformatics analysis technology to identify long non-coding RNAs related to radiosensitivity of PCaMethods In the TCGA database,the edge R package was used to detect differentially expressed lncRNAs and protein-coding genes(PCGs)in the complete response(CR)group and non-complete response(non-CR)group of PCa patients with complete radiotherapy response information,and then statistically identified the correlation between differentially expressed lncRNAs and radiosensitivity as well as these lncRNAs and PCGs.Then we used weighted gene co-expression network analysis(WGCNA)to screen the PCGs related to the radiosensitivity of PCa from those related to differentially expressed lncRNAs above.At this time,the differentially expressed PCGs detected by the edge R package,the PCGs related to the differentially expressed lncRNAs,and the WGCNA-selected PCGs related to radiosensitivity of PCa were intersected to determine the potential target genes of the selected lncRNA.Three online databases,mi Rcode,Target Scan,and DIANA,were used to predict potential target micro RNAs(mi RNAs)of selected lncRNA and mi RNAs that may regulate PCGs.Finally,reverse transcription-quantitative polymerase chain reaction(RT-q PCR)technology was used to detect the expression of selected lncRNA and target genes in samples from PCa patients randomly collected in the CR and non-CR groups.Result A total of 65 differentially expressed lncRNAs and 468 differentially expressed PCGs were detected in the PCa CR and non-CR groups of the TCGA database.By chi-square test,5 lncRNAs highly correlated with radiosensitivity were screened out of the 65 differentially expressed lncRNAs.LINC01600 with the most significant P value difference was taken as the selected lncRNA.Using Pearson correlation analysis,558protein-coding genes were found co-expressed with LINC01600.WGCNA screened darkred module containing 48 PCGs related to radiosensitivity of PCa.After intersection,three potential target genes of LINC01600 were identified,namely JUND,ZFP36 and ATF3.Most importantly,RT-q PCR was used to verify the expression of LINC01600 and JUND in our randomly collected PCa samples.In addition,we intersected the potential target mi RNA of LINC01600 and the mi RNA that may regulate JUND to build a competitive endogenous RNA(ce RNA)network.Conclusion We initially revealed the association of LINC01600 with radiosensitivity in PCa and identify its potential target PCGs for further basic and clinical research.