There are many studies on the association between miR-608 rs4919510 polymorphism and susceptibility to colorectal cancer (CRC). However, the role of rs4919510 in CRC development and its underlying mechanism remain unclear. We first evaluated the gene that may be regulated by the variation of rs4919510 through a two-stage expression quantitative trait loci analysis and then compared the expression of that identified gene in CRC tissues and adjacent nontumor tissues. Next, methyl thiazolyl tetrazolium (MTT) assay, transwell assay, and flow cytometry analyses were performed to investigate the in vitro capacity of cell proliferation, migration, invasion, apoptosis, and cell cycle of CRC cells, respectively. Finally, through bioinformatics prediction, we contrasted the regulatory network and identified microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that could regulate the obtained gene. We found that the variant G allele of rs4919510 located in miR-608 was associated with a potentially increased expression of MRPL43 in colon tissues (p = 0.065). Moreover, the results of functional experiments suggested that knockdown of the MRPL43 gene could inhibit the growth of the CRC HCT-116 cell line and promote apoptosis. Additionally, the cell cycle of CRC HCT-116 cell line was significantly arrested at the G2 phase. Next, we obtained a competing endogenous RNA regulatory network of MRPL43 with 17 pairs of miRNAs-lncRNAs by bioinformatics prediction, out of which, survival analysis indicated that different expression levels of miR-193b-3p (p = 0.0269) and miR-194-3p (p = 0.0113) were associated with overall survival in CRC patients. The rs4919510 variant G allele in miR-608 may increase the proliferation, invasion, and migration ability and decrease the apoptosis of CRC HCT-116 cell line by upregulating the expression of MRPL43, ultimately may affect the risk of CRC. Moreover, miR-193b-3p and miR-194-3p that target MRPL43 may serve as potential predictive biomarkers of CRC survival.

中文翻译：

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miR-608 rs4919510多态性可能会通过上调MRPL43表达来影响大肠癌的易感性

关于miR-608 rs4919510多态性与结直肠癌（CRC）易感性之间的关联有许多研究。但是，rs4919510在CRC开发中的作用及其潜在机制仍不清楚。我们首先通过两阶段表达定量性状基因座分析评估了可能受rs4919510变异调控的基因，然后比较了该基因在CRC组织和邻近非肿瘤组织中的表达。接下来，进行了甲基噻唑基四唑鎓（MTT）测定，transwell测定和流式细胞仪分析以研究体外CRC细胞的细胞增殖，迁移，侵袭，凋亡和细胞周期的能力。最后，通过生物信息学预测，我们对比了调控网络，并鉴定了可调控获得基因的microRNA（miRNA）和长非编码RNA（lncRNA）。我们发现位于miR-608的rs4919510变异G等位基因与结肠组织中MRPL43的潜在表达增加相关（p  = 0.065）。此外，功能实验的结果表明，MRPL43的敲低该基因可抑制CRC HCT-116细胞系的生长并促进细胞凋亡。此外，CRC HCT-116细胞系的细胞周期明显停滞在G2期。接下来，我们获得的竞争内源RNA调控网络MRPL43通过生物信息学预测与17对的miRNA-lncRNAs，外面，生存分析显示的miR-193b中-3P（的不同的表达水平p  = 0.0269）和miR-194- 3p（p  = 0.0113）与CRC患者的总体生存率相关。miR-608中的rs4919510变异G等位基因可能通过上调MRPL43的表达来增加CRC HCT-116细胞系的增殖，侵袭和迁移能力并减少其凋亡，最终可能会影响CRC的风险。此外，靶向MRPL43的miR-193b-3p和miR- 194-3p可作为CRC生存的潜在预测生物标志物。