Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Clinical Laboratory, Affiliated Tumor Hospital of Nantong University (Nantong Tumor Hospital), Nantong, China.
Mutagenesis. 2019 May 29;34(2):127-133. doi: 10.1093/mutage/gez005.
Because genetic variants in microRNAs (miRNAs) or their surrounding regions can alter miRNA processing, expression and final biological function, we investigated whether miRNA single-nucleotide polymorphisms (SNPs) are associated with cervical cancer (CC) susceptibility. Common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, miR-499 rs3746444, miR-605 rs2043556 and miR-618 rs2682818) were genotyped in the 954 patients and 1339 controls. The results showed that the miR-149 rs2292832 TC/CC genotypes were associated with a 21% increased risk of CC compared with the TT genotype [odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.00-1.47]. The association was more prominent among the subjects with age ≤ 48 years (OR = 1.55, 95% CI = 1.16-2.06), having history of abortion (OR = 1.44, 95% CI = 1.12-1.86), premenopausal status (OR = 1.41, 95% CI = 1.08-1.85) and patients with clinical stage II of CC (OR = 1.43, 95% CI = 1.08-1.90). The expression plasmids containing the pre-miR-149 sequence with C allele of rs2292832 transcribed higher amount of mature miR-149-5p/3p than these with T allele in the HeLa and SiHa cells. Therefore, the rs2292832 polymorphism might influence CC susceptibility through modulation of the procession of pre-miR-149 to mature miRNAs.
由于 microRNA（miRNA）或其周围区域的遗传变异可以改变 miRNA 的加工、表达和最终生物学功能，我们研究了 miRNA 单核苷酸多态性（SNP）是否与宫颈癌（CC）易感性相关。在 954 名患者和 1339 名对照中，对常见的 miRNA SNP（即 miR-146a rs2910164、miR-149 rs2292832、miR-196a2 rs11614913、miR-499 rs3746444、miR-605 rs2043556 和 miR-618 rs2682818）进行了基因分型。结果表明，与 TT 基因型相比，miR-149 rs2292832 TC/CC 基因型与 CC 的风险增加 21%有关[比值比（OR）=1.21，95%置信区间（CI）=1.00-1.47]。在年龄≤48 岁的患者（OR=1.55，95%CI=1.16-2.06）、有流产史（OR=1.44，95%CI=1.12-1.86）、绝经前状态（OR=1.41，95%CI=1.08-1.85）和 CC 临床分期 II 期患者（OR=1.43，95%CI=1.08-1.90）中，这种相关性更为明显。含有 rs2292832 位点 C 等位基因的 pre-miR-149 序列的表达质粒转录出的成熟 miR-149-5p/3p 比含有 T 等位基因的质粒多。因此，rs2292832 多态性可能通过调节 pre-miR-149 向成熟 miRNA 的加工过程来影响 CC 的易感性。
