关键词: Codon usage bias Lung cancer Overexpressed genes Site accessibility Translation rate miRNA-target prediction

Mesh : Binding Sites Codon Usage Collagen Type VII / genetics Humans Lung Neoplasms / genetics metabolism pathology MicroRNAs / genetics metabolism RNA, Messenger / genetics

来  源:   DOI:10.1007/s12033-022-00491-3

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.
摘要:
根据世卫组织2018年的报告,全世界有209万肺癌患者和176万人死亡。烟草仍然是造成这种致命疾病的最大危害。要执行计算分析,我们从文献中检索了过表达的肺癌基因,随后下载了其完整的编码序列(CDS).从miRBASE中提取人的成熟microRNA序列。发现了miRNA和mRNA之间的7mer-m8完美的种子匹配。过滤后,选择具有最大miRNA的结合位点的7个基因,即。,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),和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)。比较miRNA靶位点及其侧翼区域的位点可达性,平移速率,以及RSCU和tRNA之间的关系。对miRNA结合区的较高可达性和较低的翻译率表明miRNA与它们各自的靶标的结合可能是有效的。稀有密码子的存在可能进一步增强miRNA靶向。与肺癌相关的基因的密码子使用偏差研究显示核苷酸的使用不均匀和相对较高的GC含量。基因中普遍存在较低的偏见,而选择性约束主要控制了它们。最后,还揭示了靶基因的功能。可以利用miRNA的沉默特征来设计miRNA介导的疗法,该疗法可能潜在地抑制癌症中的过表达基因。
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