环状 RNA WDR26 通过 miR-212-3p 介导的错配修复基因 MSH2 调控子宫内膜癌的进展。
CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2.
机构信息
Department of Gynecological Oncology Surgery, Chenzhou First People's Hospital (The First Affiliated Hospital of Xiangnan University), No.849 Youth Avenue, Chenzhou, 423000, Hunan Province, China.
Department of Emergency, Chenzhou First People's Hospital (The First Affiliated Hospital of Xiangnan University), Chenzhou, 423000, Hunan Province, China.
出版信息
Eur J Med Res. 2022 Jul 27;27(1):135. doi: 10.1186/s40001-022-00755-3.
BACKGROUND
Circular RNAs (circRNA) are important in mediating tumor progression, but their roles in endometrial carcinoma (EC) are not fully understood yet. Many circRNAs are dysregulated and may contribute to EC progression. The functions of circWDR26 in EC remain unknown.
METHODS
The expression of circWDR26 in EC and adjacent normal tissues, and cell lines was determined by qPCR. The proliferation, apoptosis, migration, and invasion of EC cells was examined by CCK-8 assay, flow cytometry, wound healing assay and Transwell assay. The interaction between circWDR26, MSH2 and miR-212-3p was determined by luciferase assay. EC cells were inoculated into nude mice and tumor burden was determined by measuring tumor dimensions, size, and weight. The proliferative marker Ki67 in EC tissue was determined by immunohistochemistry.
RESULTS
The expression of circWDR26 in EC tissues or cell lines was higher than in the normal tissue or endometrial epithelial cells. Downregulation of circWDR26 resulted in attenuated proliferation, increased apoptosis, reduced migration and invasion of EC cells. Mechanistically, circWDR26 targeted and suppressed the expression of miR-212-3p. We further found that MSH2 was the novel target of miR-212-3p and was upregulated by circWDR26 via inhibiting miR-212-3p. In vivo experiment demonstrated that circWDR26 was essential for EC tumor growth.
CONCLUSION
circWDR26 promoted EC progression by regulating miR-212-3p/MSH2 axis and provided novel insights into anti-cancer treatment.
背景
环状 RNA（circRNA）在介导肿瘤进展中起着重要作用，但它们在子宫内膜癌（EC）中的作用尚未完全阐明。许多 circRNA 失调，可能有助于 EC 的进展。circWDR26 在 EC 中的功能尚不清楚。
方法
通过 qPCR 测定 EC 和相邻正常组织及细胞系中 circWDR26 的表达。通过 CCK-8 测定、流式细胞术、划痕愈合试验和 Transwell 试验检测 EC 细胞的增殖、凋亡、迁移和侵袭。通过荧光素酶测定确定 circWDR26、MSH2 和 miR-212-3p 之间的相互作用。将 EC 细胞接种到裸鼠中，通过测量肿瘤尺寸、大小和重量来确定肿瘤负担。通过免疫组织化学测定测定 EC 组织中增殖标志物 Ki67。
结果
EC 组织或细胞系中 circWDR26 的表达高于正常组织或子宫内膜上皮细胞。circWDR26 的下调导致 EC 细胞增殖减弱、凋亡增加、迁移和侵袭减少。机制上，circWDR26 靶向并抑制了 miR-212-3p 的表达。我们进一步发现 MSH2 是 miR-212-3p 的新靶点，circWDR26 通过抑制 miR-212-3p 而上调 MSH2。体内实验表明 circWDR26 对 EC 肿瘤生长至关重要。
结论
circWDR26 通过调节 miR-212-3p/MSH2 轴促进 EC 进展，为抗癌治疗提供了新的见解。
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