环状 RNA CEMIP 通过增强前列腺癌细胞的保护性自噬促进失巢凋亡抵抗。

CircCEMIP promotes anoikis-resistance by enhancing protective autophagy in prostate cancer cells.

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Present address: Department of Urology, Zhongnan Hospital, Wuhan University, 169 East Lake Road, Wuhan, 430061, China.

出版信息

J Exp Clin Cancer Res. 2022 Jun 2;41(1):188. doi: 10.1186/s13046-022-02381-7.

BACKGROUND

Circular RNAs (circRNAs) are essential participants in the development and progression of various malignant tumors. Previous studies have shown that cell migration-inducing protein (CEMIP) accelerates prostate cancer (PCa) anoikis resistance (AR) by activating autophagy. This study focused on the effect of circCEMIP on PCa metastasis.

METHODS

This study gradually revealed the role of circ_0004585 in PCa anoikis resistance via quantitative real-time PCR (qRT-PCR) analysis, western blotting, pull-down assays, and dual fluorescence reporter assays.

RESULTS

Functionally, circ_0004585 promoted PCa cells invasion and metastasis both in vitro and in vivo. Mechanistically, circ_0004585 directly interacted with miR-1248 to upregulate target gene expression. Furthermore, target prediction and dual-luciferase reporter assays identified transmembrane 9 superfamily member 4 (TM9SF4) as a potential miR-1248 target. Pathway analysis revealed that TM9SF4 activated autophagy to promote PCa cells anoikis resistance via mTOR phosphorylation.

CONCLUSIONS

These results demonstrated that circ_0004585 played an oncogenic role during PCa invasion and metastasis by targeting the miR-1248/TM9SF4 axis while providing new insight into therapeutic strategy development for metastatic PCa.

背景

环状 RNA（circRNAs）是各种恶性肿瘤发生和发展的重要参与者。先前的研究表明，细胞迁移诱导蛋白（CEMIP）通过激活自噬来加速前列腺癌（PCa）的失巢凋亡抗性（AR）。本研究主要关注 circCEMIP 对 PCa 转移的影响。

方法

本研究通过定量实时 PCR（qRT-PCR）分析、western blot 分析、下拉实验和双荧光报告实验，逐步揭示了 circ_0004585 在 PCa 失巢凋亡抗性中的作用。

结果

功能上，circ_0004585 在体外和体内均促进了 PCa 细胞的侵袭和转移。机制上，circ_0004585 直接与 miR-1248 相互作用，上调靶基因表达。此外，靶基因预测和双荧光素酶报告实验鉴定跨膜 9 超家族成员 4（TM9SF4）为 miR-1248 的潜在靶基因。通路分析表明，TM9SF4 通过 mTOR 磷酸化激活自噬，促进 PCa 细胞失巢凋亡抗性。