微小RNA-202通过调节SOX6的表达促进子宫内膜异位症。
MiR-202 promotes endometriosis by regulating SOX6 expression.
作者信息
Zhang Dongli, Li Yanyun, Tian Jun, Zhang Hongxia, Wang Shelian
机构信息
Obstetrics and Gynecology of The Huaihe Hospital, Henan University Kaifeng 475000, Henan, China.
出版信息
Int J Clin Exp Med. 2015 Oct 15;8(10):17757-64. eCollection 2015.
OBJECTIVES
This study is to investigate the role and mechanism of microRNA-202 (miR-202) in endometriosis.
METHODS
Forty-five cases of ectopic endometrial tissues, 25 cases of eutopic endometrial tissues and 26 cases of normal endometrial tissues were collected. MiR-202 expression was detected by quantitative RT-PCR. The protein expressions of SOX6 (sex determining region Y-box 6) and its downstream proteins (p21, cyclin D1 and pRb (retinoblastoma protein)) were detected by immunochemistry and western blot. MTT and transwell assays were used to examine cell proliferation and cell migration. The dual luciferase assay was applied to validate whether miR-202 can directly target SOX6 gene.
RESULTS
MiR-202 was highly expressed in eutopic and ectopic endometrial tissues than normal endometrial tissues (P < 0.05), and the expression was higher in tissues with III/IV stages than I/II stages (P < 0.05). The expression of SOX6 protein was lower in ectopic endometrial tissues than in normal endometrial tissues. In ectopic endometrial tissues, the expression of p21 was decreased while cyclin D1 and pRb was up-regulated than in normal endometrial tissues (P < 0.05). In cultured endometrial cells, miR-202 down-regulation induced up-regulation of SOX6 and p21 whereas down-regulation of cyclin D1 and pRb. MiR-202 promoted the proliferation and metastasis of endometrial cells. And, miR-202 could complementary bind to SOX6 3'UTR to regulate the expression of SOX6.
CONCLUSION
MiR-202 was up-regulated in the endometriosis. Through targeting SOX6 and its downstream proteins (p21, cyclin D1 and pRb), miR-202 can promote the progression of endometriosis.
目的
本研究旨在探讨微小RNA-202（miR-202）在子宫内膜异位症中的作用及机制。
方法
收集45例异位子宫内膜组织、25例在位子宫内膜组织和26例正常子宫内膜组织。采用定量逆转录聚合酶链反应（qRT-PCR）检测miR-202表达。通过免疫化学和蛋白质印迹法检测性别决定区Y框蛋白6（SOX6）及其下游蛋白（p21、细胞周期蛋白D1和视网膜母细胞瘤蛋白（pRb））的蛋白表达。采用MTT法和Transwell实验检测细胞增殖和细胞迁移。应用双荧光素酶报告基因实验验证miR-202是否能直接靶向SOX6基因。
结果
与正常子宫内膜组织相比，miR-202在在位和异位子宫内膜组织中高表达（P<0.05），且在III/IV期组织中的表达高于I/II期（P<0.05）。异位子宫内膜组织中SOX6蛋白表达低于正常子宫内膜组织。在异位子宫内膜组织中，与正常子宫内膜组织相比，p21表达降低，而细胞周期蛋白D1和pRb表达上调（P<0.05）。在培养的子宫内膜细胞中，miR-202下调诱导SOX6和p21上调，而细胞周期蛋白D1和pRb下调。miR-202促进子宫内膜细胞的增殖和转移。并且，miR-202可与SOX6 3'非翻译区（3'UTR）互补结合以调节SOX6的表达。
结论
miR-202在子宫内膜异位症中上调。通过靶向SOX6及其下游蛋白（p21、细胞周期蛋白D1和pRb），miR-202可促进子宫内膜异位症的进展。
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