METTL3 介导的 SLC38A1 的 mA 甲基化促进宫颈癌生长。

METTL3-mediated mA methylation of SLC38A1 stimulates cervical cancer growth.

机构信息

Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, 255000, China.

Department of Gynecology, Zibo Maternal and Child Health Hospital, Zibo, 255000, China.

出版信息

Biochem Biophys Res Commun. 2024 Apr 30;716:150039. doi: 10.1016/j.bbrc.2024.150039.

DOI:10.1016/j.bbrc.2024.150039

PMID:38701556

Abstract

The objective of this study was to better characterize the role of the glutamine transporter SLC38A1 in cervical cancer and explore the underlying mechanisms. Data from public databases and clinical cervical cancer tissue samples were used to assess the expression of SLC38A1 and its prognostic significance. Immunohistochemical staining, qRT-PCR, and Western blotting were used to evaluate the expression of relevant genes and proteins. Cell viability, cell cycle, apoptosis, and intracellular glutamine content were measured using CCK-8, flow cytometry, and biochemical assays. Additionally, the RNA immunoprecipitation (RIP) assay was used to examine the impact of METTL3/IGF2BP3 on the mA modification of the SLC38A1 3'UTR. Both cervical cancer specimens and cells showed significantly increased expression of SLC38A1 and its expression correlated with an unfavorable prognosis. Knockdown of SLC38A1 inhibited cell viability and cell cycle progression, induced apoptosis, and suppressed tumor growth in vivo. Glutaminase-1 inhibitor CB-839 reversed the effects of SLC38A1 overexpression. METTL3 promoted mA modification of SLC38A1 and enhanced its mRNA stability through IGF2BP3 recruitment. Moreover, METTL3 silencing inhibited cell viability, cell cycle progression, intracellular glutamine content, and induced apoptosis, but these effects were reversed by SLC38A1 overexpression. In conclusion, METTL3-mediated mA methylation of SLC38A1 stimulates cervical cancer progression. SLC38A1 inhibition is a potential therapeutic strategy for cervical cancer.

摘要

本研究旨在更深入地研究谷氨酰胺转运体 SLC38A1 在宫颈癌中的作用，并探讨其潜在机制。利用公共数据库和临床宫颈癌组织样本的数据，评估 SLC38A1 的表达及其预后意义。采用免疫组化染色、qRT-PCR 和 Western blot 检测相关基因和蛋白的表达。通过 CCK-8、流式细胞术和生化分析评估细胞活力、细胞周期、细胞凋亡和细胞内谷氨酰胺含量。此外，采用 RNA 免疫沉淀（RIP）实验研究 METTL3/IGF2BP3 对 SLC38A1 3'UTR mA 修饰的影响。宫颈癌标本和细胞均显示 SLC38A1 表达明显增加，且其表达与不良预后相关。SLC38A1 敲低抑制细胞活力和细胞周期进程，诱导细胞凋亡，并抑制体内肿瘤生长。谷氨酰胺酶-1 抑制剂 CB-839 逆转了 SLC38A1 过表达的作用。METTL3 通过 IGF2BP3 募集促进 SLC38A1 的 mA 甲基化，增强其 mRNA 稳定性。此外，METTL3 沉默抑制细胞活力、细胞周期进程、细胞内谷氨酰胺含量，并诱导细胞凋亡，但 SLC38A1 过表达可逆转这些效应。综上所述，METTL3 介导的 SLC38A1 mA 甲基化促进宫颈癌进展。SLC38A1 抑制可能是宫颈癌的一种潜在治疗策略。