Bioinformatics analyses of hsa-miR-607 and hsa-miR-641 interaction with TGFβ-RI, TGF β-RII, SMAD2, SMAD3, SAMD4 transcripts supports its regulatory effects on the TGFβ/SMAD signaling pathway

Introduction The transforming growth factor beta (TGF-β) signaling pathway plays crucial role in inflammation, immune system escape, angiogenesis and invasion /metastasis of cancer cells. The Smads are a family of intracellular mediators, has provided new Pattern for understanding mechanisms of TGF-β signaling by tumor cells. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in cell proliferation, differentiation, angiogenesis, apoptosis and tumorigenesis through targeting mRNAs. Also these molecules have been linked to cancer development, and they have been recently studied as new potential biomarkers to prognosis of tumor. In this study, we aim to find miRNAs which are targeting TGF-β/SMAD signaling crucial genes. Method To find target genes, main players of TGF-β/SMAD pathway and related miRNAs, were selected based on literature and screening among total published human miRNAs. Target prediction of miRNAs was conducted by using the online tools, TargetScan, RNA-hybrid, MiRmap and DIANA-micro-T, thus hsa-miR-607 and hsa-miR-641 were selected. Also, targeting sites of this miRNAs are evolutionary conserved on 3 -UTR of their target genes. UCSC blat tool (http://genome.ucsc.edu/) analyzed the conservation status of these MREs among animals and the predicted sequences were conserved in human, chimp, rhesus, rabbit, cow, elephant and opossum. In the next step, target genes were functionally classified and categorized in their corresponding signaling pathways by using DAVID web-site. Results We selected two miRNAs, hsa-miR-607 and hsa-miR-641 based on included criteria of abovementioned software. This miRNAs as a candidate regulators of TGFβ/SMAD signaling, because they have highest score of targeting on crucial genes. Besides, targeting sites of these two miRNAs are evolutionary conserved on 3 -UTR of their target genes. 608 / 864 Conclusions The role of the TGFβ pathway as a tumor-promoter or suppressor at the cancer cell level due to its differential effects at the early and late stages of carcinogenesis, it is still a matter of debate. Then, targeting the TGFβ pathway in cancer may be considered as a microenvironmenttargeted strategy. Numerous evidence have emphasized the essential roles of miRNAs in TGFβ/SMAD signaling pathway. Most members of the TGFβ/SMAD pathway are known to be targeted by one or more miRNA. Our bioinformatics results identified a potentially regulate of hsa-miR-607 and hsa-miR-641 in TGFβ/SMAD signaling pathway.