Li Yan, Sun Dongxia, Gao Jie, Shi Zhimin, Chi Pengyu, Meng Yuanyuan, Zou Changjun, Wang Yanhua
Department of Emergency, Handan Municipal Maternal and Child Health Hospital, Handan, Hebei, PR China.
Department of Pathology, Handan Municipal Maternal and Child Health Hospital, Handan, Hebei, PR China.
J Cell Biochem. 2019 May;120(5):8611-8618. doi: 10.1002/jcb.28149. Epub 2018 Nov 28.
In the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA-373 (miR-373) in different human cancers draw our attention. In the present research, upregulation of miR-373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR-373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/β-Catenin pathways were also investigated, which were promoted by overexpression of miR-373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR-373. LATS2 was verified as a direct target gene of miR-373 through luciferase reporter assay. Especially, the facilitation of miR-373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR-373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/β-Catenin pathway.
在女性生殖道中，子宫内膜癌是最常见的恶性肿瘤。最近，许多微小RNA（miRNA）在子宫内膜癌中的特定功能已被确定。然而，微小RNA - 373（miR - 373）在不同人类癌症中的矛盾作用引起了我们的关注。在本研究中，发现子宫内膜癌中miR - 373上调，这预示着预后不良。此外，miR - 373上调促进了子宫内膜癌细胞的迁移、侵袭和增殖。为了进一步证实该结果，还研究了上皮-间质转化（EMT）和Wnt/β-连环蛋白信号通路，它们因miR - 373过表达而被促进。然后，我们进一步研究了下游因子大肿瘤抑制激酶2（LATS2），它被miR - 373抑制。通过荧光素酶报告基因检测验证LATS2是miR - 373的直接靶基因。特别地，LATS2削弱了miR - 373对细胞增殖、迁移和侵袭的促进作用。综上所述，miR - 373通过靶向LATS2并促进EMT和Wnt/β-连环蛋白信号通路来促进子宫内膜癌的进展。
