Bioinformatic Evaluation of the Effectof rs۲۲۷۶۹۴۱ Polymorphism in Hand۲-AS۱ Gene on hasmiR-۱۲۷۵ Binding Site and Colorectal Cancer Risk

Introduction:Colorectal cancer (CRC) is the second most common adultcancer in women and the third most common in men, and it isthe fourth leading cause of cancer death, accounting for ۹.۲%of deaths worldwide. In addition to modifiable risk factors,genetic risk factors also have a significant impact on the occurrenceof CRC. Thus, identifying these genetic variants relatedto CRC risk would aid in identifying people who werepredisposed to CRC and understanding the pathogenesis ofCRC. The HAND۲-AS۱ gene is located on human chromosome۴ at q۳۴.۱. The expression of HAND۲-AS۱ was detectedby RT-PCR or capture sequencing in the plasma and tissuesof cancer patients. It has been indicated that the expression ofHAND۲-AS۱ is low in several cancers, including colorectal.HAND۲-AS۱ could suppress CRC progression by serving forhsa-miR-۱۲۷۵. Furthermore, has-miR-۱۲۷۵ could be adsorbedby lncRNAs HAND۲-AS۱ and thus inhibit the progression ofvarious cancers, including CRC.Methods: In this research we used several bioinformatic databases,including NCBI, Target scan, RNA fold, and miRbase.We check the characteristics of rs۲۲۷۶۹۴۱ on NCBI server. TheRNA fold web server will predict secondary structures of singlestranded RNA or DNA sequences. target scan and miRbase areservers for checking microRNA’s location, sequence, functionand etc.Result: Bioinformatics analysis on NCBI showed that thers۲۲۷۶۹۴۱ genetic polymorphism (C>T) located in the exonicregion of the HAND۲-AS۱ gene. RNA fold showed this polymorphismaffected the secondary structure of HAND۲-AS۱ andalso target scan and miRbase showed this polymorphism couldaffect the binding of HAND۲-AS۱ to hsa-miR-۱۲۷۵.Conclusion: Overexpression of HAND۲-AS۱ could hinder theprogression of several tumors, such as CRC. Previous studiesshowed that the rs۲۲۷۶۹۴۱ polymorphism was associatedwith CRC risk. Our research indicates that HAND۲-AS۱ geners۲۲۷۶۹۴۱ polymorphism affecting hsa-miR-۱۲۷۵ binding isassociated with a decreased risk, which may serve as a CRCsusceptibility biomarker