Mir-Pharmacogenomics Predictor Biomarkers of Metformin Effectiveness in PCOS

Background: Polycystic ovary syndrome (PCOS) is a polygenicand complex disorder of reproduction system. It is one ofthe major causes of female subfertility. Polymorphisms of thecandidate genes selected through pharmacogenomics can affectthe variable drug response among PCOS patients. These genesare regulated by microRNAs (miRNAs). MiRNAs can be deregulatedby drugs or may affect drug metabolism and thus canmodify drug response; therefore they can be used as MiR-Pharmacogenomicbiomarkers. MiR-Pharmacogenomic biomarkerscan predict the effectiveness of metformin outcome in PCOS,based on the genetic susceptibility of individuals. Analyzing theRelationships between the microRNAs, target genes and drugsfor prognostic drug response biomarker identification is availableby bioinformatics tools. The main objective of this paper isinsilico miR-Pharmacogenomics biomarker discovery of metforminoutcome evaluation in PCOS based on bioinformaticstools.Materials and Methods: PubMed articles published up to۲۰۱۸ were searched by ‘Polycystic ovarian syndrome', ‘PCOSrelated genes', ‘drug response in PCOS', ‘metformin and PCOS',‘genetic variation in PCOS and metformin outcome' keywords.Afterward, Insilico analysis by PCOSKB, Pharmaco-MiR,mTD, miRNA, miRmine and miRandola bioinformatics Toolswas implemented.Results: We used "PCOSKB" tool to obtain PCOS susceptiblegenes. High-value genes including AKR۱C۳, AMH, CGA,CYP۱A۱, HSD۱۱B۱, NR۳C۱, PI۳, PPARG, SRD۵A۲, SST andTNF were selected. "Pharmaco-miR" and "mTD" tools wereapplied to predict microRNAs based on the relationships ofmentioned genes and metformin effectiveness. RemarkablemiRNAs were miR-۱۸۱, miR-۱۹, miR-۱۲۵, miR-۹۸, miR-۵۳۹,miR-۴۵۴, miR-۱۳۸, miR-۲۷, miR-۱۳۰, miR-۳۰۱, miR-۳۲۰,miR-۳۰, miR-۱۲۴ and miR-۱۸۳. Next evaluation of these Pharmacogenomics-miRNAs followed by mimiRNA and miRminetools. In addition, the prognostic evaluation of achieved Pharmacogenomics-miRNAs as circulating biomarkers was analyzedwith miRandola tool. Further verifications indicated thatmiR-۱۲۸, miR-۳۲۰ and miR-۹۸ can be evaluated as efficientprognostic biomarkers of metformin effectiveness in PCOS individual.Conclusion: Involvement of microRNAs in drug responseprovided the capacity of identification of novel prognostic andtherapeutic biomarkers. The highly complex disease, PCOS,has a long-term complication with no exclusive (specific) treatment.The satisfactory results of identifying miR-Pharmacogenomicsbiomarkers in other complex diseases have providedhopes for the future pharmacotherapy development in PCOS.miRNA biomarkers profiling as personalized therapy can predictmetformin dosage and efficacy responses based on geneticvariation in PCOS patient. However, Further Experimentalstudies are necessary to investigate the usefulness of identifiedbiomarkers.

کلیدواژه ها:

MiR-Pharmacogenomics ، PCOS ، Biomarker ، Bioinformatics