A Study on microRNAs Targeting the Genes Overexpressed in Lung Cancer and their Codon Usage Patterns

Abstract

As reported by WHO in 2018, there were 2.09 million victims of lung cancer and 1.76 million fatalities worldwide. Tobacco remains the biggest hazard in causing this lethal disease. To execute the computational analysis, the overexpressed lung cancer genes were retrieved from literature and subsequently their complete coding sequences (CDS) were downloaded. The mature microRNA sequences of human were extracted from miRBASE. The 7mer-m8 perfect seed match between miRNAs and mRNAs was found. Following filtration, 7 genes were selected that possessed binding sites for maximum miRNAs viz., MUC5B (miR-4479, miR-1227-5p, miR-3940-5p, miR-604, miR-4455, miR-4267, miR-6750-3p, miR-4530, miR-5587-5p, miR-4508, miR-4534, miR-4443, miR-4253, miR-1321, miR-4655-5p, miR-4297, miR-4296, miR-1268a, miR-3178, miR-4750-3p, miR-1306-3p, miR-1268b, miR-3656, miR-1233-3p, miR-6804-5p), MUC16 (miR-4456, miR-1205, miR-665, miR-6808-3p, miR-1279, miR-4257, miR-1227-5p, miR-888-3p, miR-4455, miR-4267, miR-4294, miR-1275, miR-4288, miR-1178-5p, miR-4314, miR-6829-3p, miR-548av-5p, miR-1294, miR-5587-5p, miR-3622b-5p, miR-1273f, miR-4770, miR-4327, miR-4318, miR-4531, miR-4534, miR-4443, miR-7106-5p, miR-3125, miR-3650, miR-4325, miR-4266, miR-7976, miR-1290, miR-4500, miR-7160-5p, miR-4291, miR-1306-3p, miR-6130, miR-4430, miR-4725-5p, miR-4441, miR-6077, miR-1304-5p, miR-7515, miR-3182, miR-6134), COL1A1 (miR-3665, miR-1227-5p, miR-6132, miR-2861, miR-4530, miR-3155b, miR-3155a, miR-1292-3p, miR-4497), COL5A1 (miR-7162-5p, miR-3665, miR-6809-3p, miR-4313, miR-4531, miR-4532, miR-3155b, miR-4323, miR-1207-3p, miR-4260, miR-6071, miR-4710, miR-7162-5p), CELSR2 (miR-7150, miR-4308, miR-6132, miR-4770, miR-4534, miR-4492, miR-3960, miR-3178, miR-4291, miR-563), COL7A1 (miR-665, miR-6730-3p, miR-1227-5p, miR-4265, miR-6829-3p, miR-4297, miR-4532, miR-3181, miR-4310, miR-4441, miR-4497, miR-1237-3p), and FAT2 (miR-4267, miR-1275, miR-4770, miR-1825, miR-6895-5p, miR-4535, miR-4493, miR-940, miR-6861-3p, miR-4310, miR-4710, miR-4447, miR-4472). The miRNA-target site and their flank regions were compared with respect to site accessibility, translational rate, and relationship between RSCU and tRNAs. Higher accessibilities to miRNA-binding regions and lower translational rates indicated that miRNAs' binding to their respective targets might be efficient. The presence of rare codons might further augment miRNA targeting. The codon usage bias study of the genes related to lung cancer revealed non-uniform usage of nucleotides and comparatively higher GC content. Lower biasness prevailed in the genes and selective constraint mostly governed them. Lastly, the functionalities of target genes were also revealed. The silencing characteristic of miRNAs might be exploited to design miRNA-mediated therapy that might potentially repress the overexpressed genes in carcinoma.