METTL3 mediates m6A methylation modification of ULBP2 and affects the progression of cervical cancer.

IF 2.5 3区生物学

Hereditas Pub Date : 2025-07-10 DOI:10.1186/s41065-025-00483-8

Hongtao Ren, Yuting Wang, Jiao Yu, Lei An, Xiulong Ma, Jiyuan Pan

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引用次数: 0

Abstract

Background: Cervical cancer (CC) is one of the most prevalent malignancies in women, posing a significant challenge globally. However, the precise molecular mechanism regulating CC progression through methyltransferase-like protein 3 (METTL3) and UL16 Binding Protein 2 (ULBP2) remains largely unknown.

Methods: Bioinformatic analysis was used to identify the effect of ULBP2 expression in CC tissues. RT-qPCR and western blotting were employed to assess the mRNA and protein expression in CC cells and tissues. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), 5‑Ethynyl‑2'‑deoxyuridine (EdU), wound healing, and transwell assays were utilized to estimate cell viability, proliferation, and metastasis, respectively. Cell apoptosis was detected by flow cytometry. CC cells were treated with different doses of radiotherapy. The m6A level was measured using methylated RNA immunoprecipitation (MeRIP) assay. A xenograft assay was conducted to further verify the roles of ULBP2 in CC.

Results: ULBP2 was upregulated in CC. Downregulation of ULBP2 restrained the proliferation, metastasis and radiotherapy resistance of CC cells. METTL3 regulated m6A methylation modification of ULBP2. Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) promoted m6A methylation modification of ULBP2. METTL3 influenced the expression of ULBP2 and impacted the biological function of the CC cells. Silencing ULBP2 reduced the radioresistance of CC in vivo. Radiotherapy altered the gut microbiota in CC patients.

Conclusion: METTL3 modulated the m6A methylation of ULBP2, affecting the oncogenic properties and radioresistance of CC cells.

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METTL3介导ULBP2的m6A甲基化修饰，影响宫颈癌的进展。

背景：宫颈癌（CC）是女性中最常见的恶性肿瘤之一，在全球范围内构成了重大挑战。然而，通过甲基转移酶样蛋白3 （METTL3）和UL16结合蛋白2 （ULBP2）调节CC进展的确切分子机制仍然很大程度上未知。方法：采用生物信息学方法鉴定ULBP2表达对CC组织的影响。采用RT-qPCR和western blotting检测CC细胞和组织中mRNA和蛋白的表达。甲基噻唑基二苯基四唑溴化铵（MTT）、5‑乙基‑2′‑脱氧尿苷（EdU）、伤口愈合和transwell试验分别用于评估细胞活力、增殖和转移。流式细胞术检测细胞凋亡。对CC细胞进行不同剂量的放疗。采用甲基化RNA免疫沉淀（MeRIP）法测定m6A水平。结果：ULBP2在CC中表达上调，下调ULBP2可抑制CC细胞的增殖、转移和放疗抵抗。METTL3调控ULBP2的m6A甲基化修饰。胰岛素样生长因子2mrna结合蛋白1 （IGF2BP1）促进ULBP2的m6A甲基化修饰。METTL3影响ULBP2的表达，影响CC细胞的生物学功能。沉默ULBP2可降低CC在体内的放射抵抗。放疗改变了CC患者的肠道微生物群。结论：METTL3可调节ULBP2的m6A甲基化，影响CC细胞的致癌特性和放射耐药。

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.