METTL3-dependent DLG2 inhibits the malignant progression of cervical cancer by inactivating the Hippo/YAP signaling.

IF 2.7 3区生物学

Hereditas Pub Date : 2025-01-25 DOI:10.1186/s41065-025-00365-z

Mei Pu, Xia Xiao, Shasha Lv, Daqing Ran, Qian Huang, Mingming Zhou, Qirong Lei, Lingshuang Kong, Qing Zhang

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Abstract

Background: Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer and its clinical implications.

Methods: Quantitative reverse transcription polymerase chain reaction and western blotting assays were employed to detect RNA and protein expression, respectively. Colony formation assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, and transwell assays were conducted for cell functional analysis. A xenograft mouse model assay was performed to analyze tumor tumorigenesis in vivo. m6A RNA immunoprecipitation assay was used to analyze the association of METTL3 and DLG2.

Results: DLG2 was underexpressed in cervical cancer tissues and cells. Elevating DLG2 levels significantly suppressed cervical cancer cell proliferation, migration, and invasion, while promoting apoptosis. Additionally, DLG2 overexpression led to the deactivation of the Hippo/YAP signaling pathway. In vivo, DLG2 overexpression was shown to reduce tumor formation. We also discovered that METTL3 destabilized DLG2 mRNA through an m6A-dependent mechanism. Moreover, lowering DLG2 expression mitigated the effects of METTL3 silencing on cervical cancer cell malignancy.

Conclusion: DLG2 acted as a tumor suppressor in cervical cancer by inhibiting the Hippo/YAP signaling pathway. The METTL3-dependent regulation of DLG2 mRNA stability could be a critical factor in cervical cancer progression.

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mettl3依赖性DLG2通过灭活Hippo/YAP信号抑制宫颈癌的恶性进展。

背景：椎间盘大同源物2 （DLG2）与癌症发展有关，但其在宫颈癌中的作用尚不清楚。本研究旨在探讨DLG2在宫颈癌中的调控机制及其临床意义。方法：采用定量逆转录聚合酶链反应法和western blotting法分别检测RNA和蛋白的表达。采用集落形成法、5-乙基-2′-脱氧尿苷法、流式细胞术和transwell法进行细胞功能分析。采用异种移植小鼠模型实验分析肿瘤在体内的发生情况。采用m6A RNA免疫沉淀法分析METTL3与DLG2的相关性。结果：DLG2在宫颈癌组织和细胞中低表达。升高DLG2水平可显著抑制宫颈癌细胞的增殖、迁移和侵袭，同时促进细胞凋亡。此外，DLG2过表达导致Hippo/YAP信号通路失活。在体内，DLG2过表达被证明可以减少肿瘤的形成。我们还发现METTL3通过m6a依赖的机制破坏DLG2 mRNA的稳定性。此外，降低DLG2表达可减轻METTL3沉默对宫颈癌细胞恶性肿瘤的影响。结论：DLG2通过抑制Hippo/YAP信号通路在宫颈癌中发挥抑瘤作用。mettl3依赖性的DLG2 mRNA稳定性调控可能是宫颈癌进展的关键因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.

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