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.

中文翻译：

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Circ_0109046 通过 microRNA ‐105/ SOX9 /Wnt/β-catenin 轴促进子宫内膜癌细胞的恶变

新出现的证据表明环状 RNA (circRNA) 在癌症进展中的重要作用。本研究重点关注 Circ_0109046 对子宫内膜癌 (EC) 细胞恶性肿瘤的作用及其相关分子。首先，与邻近组织相比，在 EC 组织中发现 Circ_0109046 的高表达，它预示着患者的不良预后。同样，相对于正常子宫内膜上皮细胞，Circ_0109046 在 EC 细胞中的高表达得到证实。AN3-CA 细胞中 Circ_0109046 的沉默抑制了增殖和侵袭性，但增加了细胞的凋亡。Circ_0109046 主要亚定位于细胞质中，它通过海绵化 microRNA (miR)-105 介导 SOX9 的表达。Circ_0109046 下调抑制的 EC 细胞的增殖和侵袭性在 SOX9 过表达后恢复。SOX9 激活 Wnt/β-catenin 通路。此外，Circ_0109046 的下调减少了裸鼠异种移植肿瘤的生长。本研究证明 Circ_0109046 通过海绵化 miR105 上调 SOX9 的表达，导致 Wnt/β-catenin 信号通路的激活和 EC 的恶性生长。这项研究可能会为 EC 治疗提供新的认识。