LAMA3 Promotes Tumorigenesis of Oral Squamous Cell Carcinoma by METTL3-Mediated N6-Methyladenosine Modification

IF 0.8 4区医学 Q4 IMMUNOLOGY

Critical Reviews in Immunology Pub Date : 2024-01-01 DOI:10.1615/critrevimmunol.2023051066

Baoshan Ning, Yine Mei

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引用次数: 0

Abstract

Laminin subunit alpha 3 (LAMA3) is a cancer regulator. However, its effects and regulatory pathways in oral squamous cell carcinoma (OSCC) progression remain unknown. This research aimed to determine the influence of LAMA3 regulation via methyltransferase-like 3 (METTL3) on OSCC progression. Using quantitative real-time polymerase chain reaction and bioinformatics analysis, the expression levels of LAMA3 and METTL3 in OSCC tissues were examined. The functional roles of LAMA3 and METTL3 were analyzed using cell functional experiments. Using methylated RNA immunoprecipitation and mRNA stability assays, LAMA3 and METTL3 regulation was investigated. In OSCC tissues, LAMA3 was upregulated. LAMA3 inhibition hampered OSCC cell proliferation, invasion, and migration while its overexpression facilitated OSCC cell progression. METTL3 serves as a crucial upstream regulator of LAMA3 in OSCC and upregulates LAMA3 expression via an m6A-dependent mechanism. The low METTL3 expression partially restored the enhanced malignant phenotype induced by LAMA3 overexpression. Our findings indicate that METTL3 and LAMA3 act as pro-oncogenic factors in OSCC, with METTL3 promoting OSCC malignancy via m6A modification-dependent stabilization of LAMA3 transcripts, representing a novel regulatory mechanism in OSCC.

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LAMA3通过mettl3介导的n6 -甲基腺苷修饰促进口腔鳞状细胞癌的发生

层粘连蛋白亚单位- 3 (LAMA3)是一种癌症调节剂。然而，其在口腔鳞状细胞癌(OSCC)进展中的作用和调控途径尚不清楚。本研究旨在确定通过甲基转移酶样3 (METTL3)调控LAMA3对OSCC进展的影响。采用实时定量聚合酶链反应和生物信息学分析，检测LAMA3和METTL3在OSCC组织中的表达水平。通过细胞功能实验分析LAMA3和METTL3的功能作用。利用甲基化RNA免疫沉淀和mRNA稳定性分析，研究LAMA3和METTL3的调控。在OSCC组织中，LAMA3表达上调。LAMA3的抑制抑制了OSCC细胞的增殖、侵袭和迁移，而其过表达促进了OSCC细胞的进展。METTL3在OSCC中是LAMA3的重要上游调控因子，并通过m6a依赖的机制上调LAMA3的表达。低表达的METTL3部分恢复了LAMA3过表达引起的增强的恶性表型。我们的研究结果表明，METTL3和LAMA3在OSCC中作为促癌因子，其中METTL3通过m6A修饰依赖性LAMA3转录物的稳定促进OSCC恶性，代表了一种新的OSCC调节机制。

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来源期刊

Critical Reviews in Immunology 医学-免疫学

CiteScore

2.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Immunology covers a broad spectrum of investigations at the genes, molecular, cellular, organ and system levels to reveal defense mechanisms against pathogens as well as protection against tumors and autoimmune diseases. The great advances in immunology in recent years make this field one of the most dynamic and rapidly growing in medical sciences. Critical ReviewsTM in Immunology (CRI) seeks to present a balanced overview of contemporary adaptive and innate immune responses related to autoimmunity, tumor, microbe, transplantation, neuroimmunology, immune regulation and immunotherapy from basic to translational aspects in health and disease. The articles that appear in CRI are mostly obtained by invitations to active investigators. But the journal will also consider proposals from the scientific community. Interested investigators should send their inquiries to the editor before submitting a manuscript.