目的：探讨miR-206对雌激素诱导的ER-α36阳性胃癌（gastric cancer, GC）细胞BGC-823增殖和侵袭的影响及其相关 机制。方法: 用不同浓度（1、10和100 pmol/L）的雌二醇（estradiol，E2）刺激ER-α36阳性BGC-823细胞后，用qPCR法检测miR-206 表达水平，MTT法和Transwell实验分别检测细胞的增殖和侵袭能力，WB法检测细胞中CDK14的表达。将miR-206 mimic、 miR-NC、pcDNA-CDK14、pcDNA-vector 等转染 ER- α36 阳性 BGC-823 细胞 ，并给予 100 pmol/L 的 E2 处理后 ，用 MTT 法和 Transwell小室法分别检测细胞的增殖和侵袭能力，WB法检测细胞中CDK14的表达。用双荧光素酶报告基因实验验证miR-206 与CDK14之间的靶向关系。结果: E2能显著降低ER-α36阳性BGC-823细胞中miR-206表达水平（P<0.05或P<0.01）、增强细胞 的增殖和侵袭能力（P<0.05或P<0.01）、上调细胞中CDK14的表达水平（P<0.01）。过表达miR-206能显著降低E2诱导的ER-α36 阳性BGC-823细胞的增殖和侵袭能力（均P<0.01）。miR-206通过直接结合CDK14 mRNA的3'-UTR发挥抑制作用，从而负向调 节CDK14的表达，进而抑制ER-α阳性BGC-823细胞的增殖和侵袭能力（均P<0.01）。结论: miR-206通过靶向CDK14从而抑制 雌激素诱导的ER-α36阳性GC细胞的增殖和侵袭。

Objective: To explore the effects of miR-206 on the proliferation and invasion of ER-α36-positive gastric cancer (GC) BGC-823 cells induced by estrogen and its related mechanisms. Methods: ER- α36-positive BGC-823 cells were stimulated with estradiol (E2) at different concentrations (1, 10 and 100 pmol/L), then, the expression level of miR-206 was detected by qPCR, the proliferation and invasion were respectively determined by MTT and Transwell assays, and the expression of cyclin-dependent kinase 14 (CDK14) protein was detected by WB. After transfecting miR-206 mimic, miR-NC, pcDNA-CDK14 or pcDNA-vector into ER-α36 positive BGC-823 cells and stimulating them with 100 pmol/L E2, the proliferation and invasion ability of the cells were respectively detected by MTT assay and Transwell assays, and the expression of CDK14 was detected by WB assay. The targeting relationship between miR-206 and CDK14 was verified by Dual luciferase reporter gene assay. Results: E2 significantly decreased the expression level of miR-206 (P<0.05 or P<0.01), enhanced the proliferation and invasion (P<0.05 or P<0.01), and up-regulated the expression level of CDK14 （P<0.01) in ER-α36-positive BGC-823 cells. Overexpression of miR-206 could significantly reduce the proliferation and invasion ability of ER-α36-positive BGC-823 cells induced by E2 (all P<0.01). miR-206 negatively regulated the expression of CDK14 by directly binding to the 3'-UTR of CDK14 mRNA, thereby inhibiting the proliferation and invasion of ER- α -positive BGC-823 cells (all P<0.01). Conclusion: miR-206 inhibits the proliferation and invasion of estrogen-induced ER- α36-positive GC cells by targeting CDK14.

安徽 省 自 然 科 学基金资助项目（No. 1908085QH333）