Department of Epidemiology, School of Public Health, Nantong University, Nantong, China.
Department of Oncology, Changshu No. 1 People's Hospital, Suzhou, China.
DNA Cell Biol. 2020 Nov;39(11):2017-2027. doi: 10.1089/dna.2020.5689. Epub 2020 Oct 13.
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 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 in colon tissues ( = 0.065). Moreover, the results of functional experiments suggested that knockdown of the 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 with 17 pairs of miRNAs-lncRNAs by bioinformatics prediction, out of which, survival analysis indicated that different expression levels of miR-193b-3p ( = 0.0269) and miR-194-3p ( = 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 , ultimately may affect the risk of CRC. Moreover, miR-193b-3p and miR-194-3p that target may serve as potential predictive biomarkers of CRC survival.
有许多关于 miR-608 rs4919510 多态性与结直肠癌（CRC）易感性之间关联的研究。然而，rs4919510 在 CRC 发展中的作用及其潜在机制尚不清楚。我们首先通过两阶段表达数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 CRC 组织和相邻非肿瘤组织中该鉴定基因的表达。接下来，通过噻唑蓝（MTT）检测、Transwell 检测和流式细胞术分析，分别研究了 CRC 细胞的增殖、迁移、侵袭、凋亡和细胞周期能力。最后，通过生物信息学预测，我们对比了调控网络，确定了可调控获得基因的 microRNAs（miRNAs）和长链非编码 RNA（lncRNAs）。我们发现，rs4919510 中的变异 G 等位基因位于 miR-608 中，与结肠组织中 的潜在高表达相关（ = 0.065）。此外，功能实验结果表明，下调 基因可抑制 CRC HCT-116 细胞系的生长并促进凋亡。此外，CRC HCT-116 细胞系的细胞周期明显被阻滞在 G2 期。接下来，我们通过生物信息学预测获得了与 有 17 对 miRNA-lncRNA 的竞争内源性 RNA 调控网络，其中，生存分析表明，miR-193b-3p（ = 0.0269）和 miR-194-3p（ = 0.0113）的不同表达水平与 CRC 患者的总生存相关。miR-608 中的 rs4919510 变异 G 等位基因可能通过上调 的表达，增加 CRC HCT-116 细胞系的增殖、侵袭和迁移能力，降低凋亡能力，最终可能影响 CRC 的风险。此外，靶向 的 miR-193b-3p 和 miR-194-3p 可能作为 CRC 生存的潜在预测生物标志物。
