一种针对肺癌中高表达基因的 microRNAs 及其密码子使用模式的研究。
A Study on microRNAs Targeting the Genes Overexpressed in Lung Cancer and their Codon Usage Patterns.
机构信息
Department of Biotechnology, Assam University, Silchar, 788011, Assam, India.
出版信息
Mol Biotechnol. 2022 Oct;64(10):1095-1119. doi: 10.1007/s12033-022-00491-3. Epub 2022 Apr 18.
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.
据世界卫生组织 2018 年报告，全球有 209 万肺癌患者和 176 万人死亡。烟草仍然是导致这种致命疾病的最大危害。为了执行计算分析，从文献中检索出过度表达的肺癌基因，随后下载它们的完整编码序列（CDS）。从 miRBASE 中提取出人类的成熟 microRNA 序列。发现 microRNA 和 mRNAs 之间的 7mer-m8 完美种子匹配。经过过滤，选择了 7 个具有最大 microRNA 结合位点的基因，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）。miRNA 靶位点及其侧翼区域在靶位可及性、翻译率以及与 RSCU 和 tRNAs 的关系方面进行了比较。miRNA 结合区具有较高的可及性和较低的翻译率表明，miRNA 与其各自的靶标结合可能是有效的。稀有密码子的存在可能进一步增强 miRNA 的靶向性。与肺癌相关基因的密码子使用偏性研究表明，核苷酸的使用不均匀，GC 含量相对较高。基因中存在较低的偏倚，选择压力主要控制它们。最后，还揭示了靶基因的功能。miRNA 的沉默特性可能被利用来设计 miRNA 介导的治疗，该治疗可能潜在地抑制癌中的过表达基因。
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