microRNA-based targeting of Kruppellikefactor ۴ in prostate cancer: A bioinformatics analysis

Background: A large body of evidence has shown that microRNAs(miRNAs), small non-coding endogenous RNAs, controlgene expression and play important roles in tumorigenesis. Upregulationof miR-۷-۵p was found to be involved in the developmentof human malignancies such as cancer. KLF۴, a protein-coding gene belonging to the Kruppel family, play a role asan oncogene in different type of cancer such as prostate cancer.Here, we investigated the ability of miR-۷-۵p as a miRNA thattargets KLF۴.Materials and Methods: To verify the possible regulation ofKLF۴ by miR-۷, several in silico tools such as TargetScan,miRDB and RNAHybrid were used. Functional enrichmentanalysis was carried out by DIANA-miRPath.Results: Using TargetScan tool, we uncovered different miRNAsthat have binding sites (MREs: miRNA response elements)in the ۳’-UTR of KLF۴. Among different miRNAs,miR-۷-۵p was a miRNA that potentially target KLF۴ and takepart in different aspect of tumor progression. Being KLF۴ an insilico predicted target of miR-۷-۵p, we decided to verify its targetingby two other algorithmic tools, miRDB and RNAhybrid.Our survey showed that miR-۷-۵p targets KLF۴ by binding asequence located at ۶۶ to ۷۲ positions of the ۳’ UTR of KLF۴.RNAhybrid prediction showed miR-۷-۵p potentially binds tothe ۳’UTR of KLF۴ with the minimum free energy of -۲۳.۸kcal/mol. In addition, many pairs of bases are formed between۵’ of KLF۴ and ۳’ of miR-۷-۵p , which increases the interactionbetween these two. Additionally, using the ‘Gene and PathwayUnion Analysis’ option of DIANA‐miRPath v.۳.۰, we demonstratedthat the miR-۷-۵p may contribute to different cell signalingaltered in human cancers including prostate cancer.Conclusion: We hypothesized the ability of miR-۷-۵p as amiRNA targeting the protein-coding gene, KLF۴, and suggestedits functional role in regulating signaling pathways involvedin prostate cancer pathogenesis.

کلیدواژه ها:

Prostate cancer ، Bioinformatics ، miR-۷ ، KLF۴