Department 1 of Gynecological Oncology, Jilin Cancer Hospital, Changchun, China.
Department of Radiotherapy of Gynecologic Oncology, Jilin Cancer Hospital, Changchun, China.
IUBMB Life. 2021 Jan;73(1):159-176. doi: 10.1002/iub.2415. Epub 2020 Nov 21.
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.
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。
