Downregulated miRNA-1269a variant (rs73239138) decreases the susceptibility to gastric cancer via targeting ZNF70
Downregulated miRNA-1269a variant (rs73239138) decreases the susceptibility to gastric cancer via targeting ZNF70
复制标题
下调的 miRNA-1269a 变体 (rs73239138) 通过靶向 ZNF70 降低对胃癌的易感性
DOI：
10.3892/ol.2017.7091
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发表时间：
2017-12-01
期刊：
影响因子：
2.9
通讯作者：
Liu, Jie
中科院分区：
文献类型：
--
作者：
Li, Wenshuai;Zhang, Huilu;Liu, Jie
尽管新的证据表明 microRNA (miRNA) 中的单核苷酸多态性 (SNP) 与胃癌易感性相关，但有限的研究揭示了潜在的分子机制。在本研究中，结果表明miR-1269a rs73239138具有降低胃癌风险的作用。与胃细胞中的野生型miR-1269a相比，miR-1269a变异表达水平显着下调（图1）。此外，miR-1269a的过度表达抑制胃癌细胞的凋亡。 miR-1269a 变体的表达通过增加细胞凋亡率来抑制 miR-1269a 的功能，并且 Bik、Bim 和 Bak 的表达持续上调。此外，锌指蛋白70（ZNF70）被确定为miR-1269a的靶基因，其被miR-1269a下调并被miR-1269a变体上调。 ZNF70 被证明在胃癌中发挥肿瘤抑制作用。据我们所知，本研究首次强调了miR-1269a变体rs73239138通过下调其表达和靶向ZNF70（促进胃癌细胞凋亡）来降低胃癌易感性的关键作用。该 SNP 有望作为胃癌的潜在生物标志物和治疗靶点。
Although emerging evidence has indicated that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are associated with susceptibility to gastric cancer, a limited number of studies have revealed the underlying molecular mechanisms. In the present study, the results suggested that miR-1269a rs73239138 has a role in decreasing the risk of gastric cancer. The level of miR-1269a variant expression was significantly downregulated compared with the wild-type miR-1269a in the gastric cells (Fig. 1). Furthermore, overexpression of miR-1269a inhibited apoptosis of gastric cancer cells. Expression of the miR-1269a variant inhibited the function of miR-1269a by increasing the apoptotic rate and the expression of Bik, Bim and Bak was upregulated consistently. In addition, zinc-finger protein 70 (ZNF70) was identified to be a target gene of miR-1269a, which was downregulated by miR-1269a and upregulated by miR-1269a variant. ZNF70 was indicated to exert a role as a tumor suppressor in gastric cancer. To the best our knowledge, the present study for the first time highlights a critical role of miR-1269a variant rs73239138 in decreasing the susceptibility to gastric cancer by downregulating its expression and targeting ZNF70, which promotes apoptosis of gastric cancer cells. This SNP is indicated to serve as a potential biomarker and therapeutic target for gastric cancer.