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环状 RNA 0109046 通过 microRNA-105/SOX9/Wnt/β-catenin 轴促进子宫内膜癌细胞的恶性转化。

Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA-105/SOX9/Wnt/β-catenin axis.

机构信息

Department 1 of Gynecological Oncology, Jilin Cancer Hospital, Changchun, China.

Department of Radiotherapy of Gynecologic Oncology, Jilin Cancer Hospital, Changchun, China.

出版信息

IUBMB Life. 2021 Jan;73(1):159-176. doi: 10.1002/iub.2415. Epub 2020 Nov 21.

Abstract

Emerging evidence suggests the important involvements of circular RNAs (circRNAs) in cancer progression. This study focuses on the function of Circ_0109046 on the malignancy of endometrial carcinoma (EC) cells and the molecules involved. First, high expression of Circ_0109046 was found in EC tissues compared to the adjacent tissues, and it predicted unfavorable prognosis in patients. Similarly, high expression of Circ_0109046 was confirmed in EC cells relative to that in normal endometrial epithelial cells. Silencing of Circ_0109046 in AN3-CA cells inhibited proliferation and aggressiveness but increased apoptosis of cells. Circ_0109046 was mainly sub-localized in cytoplasm, and it mediated SOX9 expression through sponging microRNA (miR)-105. The proliferation and aggressiveness of EC cells suppressed by Circ_0109046 downregulation was recovered upon SOX9 overexpression. SOX9 activated the Wnt/β-catenin pathway. Furthermore, downregulation of Circ_0109046 reduced the growth of xenograft tumors in nude mice. This study evidenced that Circ_0109046 upregulates SOX9 expression through sponging miR105, leading to activation of Wnt/β-catenin signaling and the malignant growth of EC. This study may offer novel understanding in EC treatment.

摘要

新出现的证据表明,环状 RNA(circRNAs)在癌症进展中起着重要作用。本研究重点关注 Circ_0109046 对子宫内膜癌(EC)细胞恶性行为的功能及其涉及的分子。首先,与相邻组织相比,EC 组织中 Circ_0109046 的表达水平较高,且患者的预后较差。同样,与正常子宫内膜上皮细胞相比,EC 细胞中 Circ_0109046 的表达水平也较高。在 AN3-CA 细胞中沉默 Circ_0109046 可抑制细胞增殖和侵袭,同时增加细胞凋亡。Circ_0109046 主要定位于细胞质,通过海绵吸附 microRNA(miR)-105 介导 SOX9 表达。Circ_0109046 下调后抑制的 EC 细胞的增殖和侵袭能力可通过过表达 SOX9 得到恢复。SOX9 激活了 Wnt/β-catenin 通路。此外,Circ_0109046 的下调可减少裸鼠异种移植瘤的生长。本研究表明,Circ_0109046 通过海绵吸附 miR105 上调 SOX9 表达,从而激活 Wnt/β-catenin 信号通路,促进 EC 的恶性生长。本研究可能为 EC 的治疗提供新的认识。

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