Chen Xueya, Yan Zhiling, Liu Weipeng, Guo Lili, Xu Jinmei, Shi Li, Yao Yufeng
Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People's Republic of China.
Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
Int J Gen Med. 2024 Sep 16;17:4171-4188. doi: 10.2147/IJGM.S473133. eCollection 2024.
Cervical cancer (CC) poses a significant threat to women's health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC.
A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method.
The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01-0.39; OR = 0.61, 95% CI: 0.49-0.76) and CC (OR = 0.08, 95% CI: 0.01-0.66; OR = 0.71, 95% CI: 0.59-0.86), respectively.
Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.
宫颈癌（CC）对全球女性健康构成重大威胁，已证实多种信号通路参与其发展。AMPK信号通路在维持能量稳态中起核心作用，其失调与CC的发生密切相关。微小RNA（miRNA）表达水平的变化可能与AMPK信号通路有关。单核苷酸多态性（SNP）可影响miRNA的功能并导致CC的发生。为了研究AMPK通路相关miRNA的SNP与中国汉族人群CC之间的关联，我们选择了位于AMPK通路中的8个miRNA基因，并分析了这些基因内的9个SNP位点，以探讨它们是否与宫颈上皮内瘤变（CIN）和CC的遗传易感性相关。
本研究共纳入2220名受试者，包括928名健康对照者、421名CIN患者和871名CC患者。使用TaqMan方法对9个候选SNP（miR-27a中的rs895819、miR-449b中的rs10061133、miR-216a中的rs41291179、miR-182中的rs76481776、miR-5196中的rs10406069、miR-612中的rs12803915和rs550894、miR-3622b中的rs66683138以及miR-627中的rs2620381）进行基因分型。
结果显示，rs41291179和rs12803915的等位基因分布在对照组与CIN组之间以及对照组与CC组之间存在显著差异（所有P值<0.005）。rs41291179的A等位基因和rs12803915的G等位基因分别与CIN（OR = 0.05，95%CI：0.01 - 0.39）和CC（OR = 0.08，95%CI：0.01 - 0.66）以及CIN（OR = 0.61，95%CI：0.49 - 0.76）和CC（OR = 0.71，95%CI：0.59 - 0.86）的风险降低相关。
我们的结果表明，AMPK信号通路的miRNA基因多态性与CC的发生有关。
