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PDS5B通过与YTHDC1结合来正向调节PTEN,从而抑制子宫内膜癌的恶性进展。

PDS5B positively regulates PTEN by binding to YTHDC1 to inhibit the malignant progression of endometrial carcinoma.

作者信息

Wang Hanyi, Qian Yaping, Li Jie, Gao Qianyun

机构信息

Department of Obstetrics and Gynecology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou No. 7 People's Hospital, Changzhou, 213000, Jiangsu, China.

出版信息

Discov Oncol. 2025 Jul 1;16(1):1192. doi: 10.1007/s12672-025-03021-0.

DOI:10.1007/s12672-025-03021-0
PMID:40591192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12214172/
Abstract

BACKGROUND

Endometrial carcinoma (EC) is a common gynecological malignancy with a complex pathogenesis. PDS5B is revealed to be dysregulated and play critical roles in multiple cancers, while its role in EC remains largely unknown. The aim of this study was to explore the expression profile and biological function of the PDS5B in EC.

METHODS

In this study, differential gene expression analysis in EC was performed using public databases and relevant analytical tools. The expression of PDS5B was verified by western blot and qRT-PCR in cell and tissue samples. The effects of PDS5B overexpression on EC cell proliferation, invasion and apoptosis, as well as the interaction of PDS5B with YTHDC1 and the regulation of PTEN stability were further explored by in vitro experiments. The effects of PDS5B on tumorigenesis and metastasis were explored using in vivo models.

RESULTS

PDS5B was down-regulated in EC, and overexpression of PDS5B significantly inhibited cell growth, and promoted apoptosis. In vitro results revealed that PDS5B interacted with YTHDC1 in EC cells and YTHDC1 regulated PTEN expression and stability via m6A modification, affecting the biological behavior of EC cells. In in vivo nude mouse models, overexpression of PDS5B significantly inhibited EC tumor development and metastasis in nude mice.

CONCLUSIONS

PDS5B interacts with YTHDC1 and further regulates PTEN in endometrial cancer cells, thereby inhibiting the malignant development of the tumor. These findings indicate the potential part of PDS5B in the development of EC and provide new molecular targets for the treatment of EC.

摘要

背景

子宫内膜癌(EC)是一种常见的妇科恶性肿瘤,发病机制复杂。研究发现PDS5B在多种癌症中表达失调并发挥关键作用,但其在EC中的作用尚不清楚。本研究旨在探讨PDS5B在EC中的表达谱及生物学功能。

方法

本研究利用公共数据库和相关分析工具对EC进行差异基因表达分析。通过蛋白质免疫印迹法和qRT-PCR在细胞和组织样本中验证PDS5B的表达。通过体外实验进一步探讨PDS5B过表达对EC细胞增殖、侵袭和凋亡的影响,以及PDS5B与YTHDC1的相互作用和对PTEN稳定性的调控。利用体内模型探讨PDS5B对肿瘤发生和转移的影响。

结果

PDS5B在EC中表达下调,PDS5B过表达显著抑制细胞生长并促进凋亡。体外实验结果显示,PDS5B在EC细胞中与YTHDC1相互作用,YTHDC1通过m6A修饰调节PTEN表达和稳定性,影响EC细胞的生物学行为。在体内裸鼠模型中,PDS5B过表达显著抑制裸鼠EC肿瘤的发展和转移。

结论

PDS5B与YTHDC1相互作用并进一步调节子宫内膜癌细胞中的PTEN,从而抑制肿瘤的恶性发展。这些发现揭示了PDS5B在EC发生发展中的潜在作用,为EC的治疗提供了新的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/17ea7456a605/12672_2025_3021_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/6141e58d841b/12672_2025_3021_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/0b973a42b3f3/12672_2025_3021_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/88a05e6d7c89/12672_2025_3021_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/fd3c9ed6e308/12672_2025_3021_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/3313f6585371/12672_2025_3021_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/17ea7456a605/12672_2025_3021_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/6141e58d841b/12672_2025_3021_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/0b973a42b3f3/12672_2025_3021_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/88a05e6d7c89/12672_2025_3021_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/fd3c9ed6e308/12672_2025_3021_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/3313f6585371/12672_2025_3021_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8757/12214172/17ea7456a605/12672_2025_3021_Fig6_HTML.jpg

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