Institute of Biomedical and Genetic Engineering (IBGE), 24- Mauve Area, G-9/1, Islamabad Pakistan.
Department of Zoology, PMAS-Arid Agriculture University, Rawalpindi, Pakistan.
Cell Mol Biol (Noisy-le-grand). 2020 Oct 31;66(7):169-173.
Colorectal cancer is a life-threatening and therapeutically challenging disease. Increasingly it is being deciphered that genetic and epigenetic mutations play a central role in cancer onset and progression. Excitingly, discovery of non-coding RNAs is considered to be a milestone in molecular oncology and emerging evidence is deepening our understanding about pivotal role of miRNAs in carcinogenesis. miR-143 has been experimentally verified to play an instrumental role as tumor suppressor. Recent studies suggest that single nucleotide polymorphisms rs41291957 and rs353292 in miR-143 may associate with the progression and or development of colorectal cancer. In present study 400 Pakistani subjects participated including 200 colorectal cancer patients and 200 age and gender matched healthy individuals. Blood samples and clinical information of the confirmed patients was collected from cancer diagnosis and treatment hospitals in Pakistan. The polymorphisms rs41291957 and rs353292 were genotyped in patients and controls by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were validated by Sanger sequencing. The association of the SNPs within the study group was analyzed by χ² test with p value < 0.05 as significant. Odds ratio was calculated with 95% confidence interval.Genetic predisposition to cancer was observed in presence of characteristic rs45291957 polymorphism. χ² test results show strongly significant association mi-RNA rs45291957 SNP with colorectal cancer p value 0.0111 (<0.05) along with the statistically significant correlation tested by odds ratio with 95% confidence interval. However, no significant correlation (p value 0.6683) could be found for the association of rs353292 with colorectal cancer in Pakistani population. The present study for the first time gave evidence of miR-143 rs41291957 involvement in colorectal cancer patients of Pakistani population. This target can be a useful molecular tool for the prognosis and treatment targets for colorectal cancer in Pakistani population. rs353292 genetic association can be explored for different cancers in Pakistan to completely rule out its role in cancer.
结直肠癌是一种危及生命且治疗极具挑战性的疾病。越来越多的证据表明，遗传和表观遗传突变在癌症的发生和发展中起着核心作用。令人兴奋的是，非编码 RNA 的发现被认为是分子肿瘤学的一个里程碑，新的证据加深了我们对 miRNA 在致癌作用中的关键作用的理解。miR-143 已被实验证实作为肿瘤抑制因子发挥作用。最近的研究表明，miR-143 中的单核苷酸多态性 rs41291957 和 rs353292 可能与结直肠癌的进展和/或发展有关。在本研究中，共有 400 名巴基斯坦受试者参与，其中包括 200 名结直肠癌患者和 200 名年龄和性别匹配的健康个体。从巴基斯坦的癌症诊断和治疗医院收集了确诊患者的血液样本和临床信息。在患者和对照组中，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对 rs41291957 和 rs353292 多态性进行了基因分型，并通过 Sanger 测序进行了验证。在研究组中，通过 χ²检验分析了 SNP 的相关性，p 值 < 0.05 为显著。用 95%置信区间计算比值比。观察到存在特征性 rs45291957 多态性时存在癌症遗传易感性。 χ²检验结果显示，miR-NA rs45291957 SNP 与结直肠癌显著相关，p 值为 0.0111（<0.05），同时通过 95%置信区间的比值比进行了统计学相关性检验。然而，在巴基斯坦人群中，rs353292 与结直肠癌的相关性没有显著相关性（p 值为 0.6683）。本研究首次为 miR-143 rs41291957 参与巴基斯坦人群结直肠癌患者提供了证据。该靶点可作为巴基斯坦人群结直肠癌预后和治疗靶点的有用分子工具。rs353292 遗传相关性可在巴基斯坦不同癌症中进行探索，以完全排除其在癌症中的作用。
