مقالات پذیرفته شده در سومین کنگره بین المللی زیست پزشکی
Bioinformatics approach of relation between hsa-mir-144, GATA3 gene, rs104894164 and lnc-ATXN1L-1:1 with lung cancer
Bioinformatics approach of relation between hsa-mir-144, GATA3 gene, rs104894164 and lnc-ATXN1L-1:1 with lung cancer
Anasik Karabedianhajiabadi,1,*Negar Balmeh,2
1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran 2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
Introduction: Introduction: In recent years, lung cancer as its high prevalence has gained attention of researchers. One key factor behind this fact is genetic material, miRNA, which plays important role in tumor development and progression. The another aspects of cancer occurrence are sequence variations, SPNs and long noncoding RNAs (lncRNAs) as potentially new and crucial layers of biological regulations. Based on studies on lung cancer, hsa-mir-144 of chromosome 17th has been selected for this approach.
Methods: Materials and Methods: In this study, a large scale of bioinformatics analysis such as, miRBase, miRTarBase, miRWALK, GEPIA2, NCBI, DAVID, USCS, RNAhybrid and GeneMANIA databases are used to get required data about microRNA basis, validated and predicted target genes, genes expressions, signaling pathways, SNP and relation between genes as an intermediate network.
Results: Result: Based on hsa-mir-144 targets it has been revealed that MAPK1, PIK3R1, EGFR and GATA3 genes are the most frequent genes which play essential role in Small Cell Lung Cancer, Focal Adhesion and PI3K-AKT Signaling pathways that all follow the same pattern. By occurring of rs104894164 in GATA3 gene, as a vital gene in cancer, interaction between hsa-mir-144 and GATA3 increases, thus probably this event triggers lung cancer process.
Conclusion: Conclusion: According to the studies FAK gene, which has been operated by ITGA, ITGB and RTK cell surface receptors, activates PI3K gene. By activation of PI3K gene that changes PIP2 to PIP3, AKT gene starts its function to agitate NF-kB via regulating IKK that result in transcription of pro-survival genes. Under various circumstances, activation of MAPK1 was shown to trigger cell survival indirectly. Accordingly, all foresaid genes, targets of the microRNA, lead to cell cycle advancement and cancer. Moreover, rs104894164 in GATA3 gene, as a critical transcription factor, leads to hsa-mir-144 and GATA3 interaction abundance. Hsa-mir-144 acts as a tumor suppressor for GATA3 gene, so if rs104894164 happens in this gene, the interaction between microRNA and the gene will be induced. In addition, various researches have revealed that lnc-ATXN1L-1:1 of hsa-mir-144 is able to connect to this microRNA which based on RNAhybrid data it has been defined that because this lnc sticks to the microRNA, could eradicate the interaction between microRNA and GATA3 gene, and acts unlike of SNP. So the microRNA loss its Inhibitory effect on the gene. Evidences suggest that all the mentioned events help angiogenesis and cell proliferation, that outcome in lung cancer excessing which cause the metastatic process of lung cancer indirectly. These findings might provide a promising therapy for clinical treatment of lung cancer.