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长链非编码RNA DEPDC1-AS1通过调控miR-508-3p促进子宫内膜癌进展。

LncRNA DEPDC1-AS1 drives the progression of endometrial carcinoma by regulating miR-508-3p.

作者信息

Wang Rencheng, Ji Jianhua

机构信息

Department of Obstetrics and Gynecology, Renhe Hospital, No. 1999, Changjiang West Road, Baoshan District, Shanghai, 200431, China.

出版信息

Discov Oncol. 2025 Sep 26;16(1):1721. doi: 10.1007/s12672-025-03417-y.

Abstract

OBJECTIVE

Endometrial carcinoma (EC) ranks among the three most prevalent malignant tumors affecting the female reproductive system. DEPDC1-AS1 is a newly identified lncRNA, and its mechanism of action in EC remains to be explored.

METHODS

100 hyperplasia and 100 EC patients were included. The abundance of DEPDC1-AS1, miR-508-3p, and SQSTM1 was quantified by qRT-PCR. Kaplan-Meier survival curve and Cox regression predicted prognostic factors. Pearson correlation was used to assess the relationships among the molecular markers. Cell proliferation was assessed with the CCK-8 assay, and migration/invasion with Transwell assays. The regulatory interactions were predicted by bioinformatics and validated through dual-luciferase reporter assays and co-transfection experiments.

RESULTS

DEPDC1-AS1 was enhanced in EC tissues and cell lines and identified as an independent prognostic factor. Its expression was associated with FIGO stage and cervical invasion, while lower DEPDC1-AS1 levels correlated with improved survival outcomes. Functional experiments showed that silencing DEPDC1-AS1 inhibited EC cell proliferation, migration, and invasion. Mechanistically, DEPDC1-AS1 sponges miR-508-3p, with a confirmed negative correlation between the two. DEPDC1-AS1 promoted EC cell aggressiveness by modulating miR-508-3p, which directly targets SQSTM1. SQSTM1 expression was negatively correlated with miR-508-3p and positively correlated with DEPDC1-AS1.

CONCLUSION

DEPDC1-AS1 may serve as a promising prognostic biomarker in EC. These findings suggest that DEPDC1-AS1 facilitates EC progression through the miR-508-3p, highlighting its potential as a therapeutic target.

摘要

目的

子宫内膜癌(EC)是影响女性生殖系统的三大常见恶性肿瘤之一。DEPDC1-AS1是一种新发现的长链非编码RNA(lncRNA),其在EC中的作用机制尚待探索。

方法

纳入100例增生患者和100例EC患者。通过qRT-PCR定量检测DEPDC1-AS1、miR-508-3p和SQSTM1的丰度。采用Kaplan-Meier生存曲线和Cox回归预测预后因素。用Pearson相关性分析评估分子标志物之间的关系。用CCK-8法评估细胞增殖,用Transwell法评估迁移/侵袭能力。通过生物信息学预测调控相互作用,并通过双荧光素酶报告基因检测和共转染实验进行验证。

结果

DEPDC1-AS1在EC组织和细胞系中表达增强,并被确定为独立的预后因素。其表达与国际妇产科联盟(FIGO)分期和宫颈浸润相关,而较低的DEPDC1-AS1水平与较好的生存结果相关。功能实验表明,沉默DEPDC1-AS1可抑制EC细胞的增殖、迁移和侵袭。机制上,DEPDC1-AS1作为miR-508-3p的海绵,二者呈负相关。DEPDC1-AS1通过调控miR-508-3p促进EC细胞的侵袭性,miR-508-3p直接靶向SQSTM1。SQSTM1的表达与miR-508-3p呈负相关,与DEPDC1-AS1呈正相关。

结论

DEPDC1-AS1可能是EC中有前景的预后生物标志物。这些发现表明,DEPDC1-AS1通过miR-508-3p促进EC进展,凸显了其作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c8c/12474827/2f60ace2922f/12672_2025_3417_Fig1_HTML.jpg

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