METTL14‑mediated RNA methylation in digestive system tumors

Hu, Jiexuan; Lin, Huiyun; Wang, Wenwen; Su, Qiang; Cao, Bangwei

doi:10.3892/ijmm.2023.5289

Cited by 4 publications

(1 citation statement)

References 123 publications

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“…However, its expression is downregulated in various tumors, including hepatocellular carcinoma, bladder cancer, endometrial carcinoma, and glioblastoma, where it functions as a tumor suppressor. 39 , 40 Moreover, in digestive malignant tumors, METTL14 has been observed to play a contradictory role in the regulation of digestive system tumors, 41 with similar findings reported in the studies related to OC. Trophinin-associated protein (TROAP, also known as TASTIN) has been implicated in the proliferation, invasion, and migration processes of various cancers.…”

Section: Introductionsupporting

confidence: 73%

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer

Zhang,

Ling,

Zhou

et al. 2024

Cancer Control

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Ovarian cancer (OC) is the most lethal gynecological tumor, characterized by its insidious and frequently recurring metastatic progression. Owing to limited early screening methods, over 70% of OC cases are diagnosed at advanced stages, typically stage III or IV. Recently, N6-methyladenosine (m6A) modification has emerged as a hotspot of epigenetic research, representing a significant endogenous RNA modification in higher eukaryotes. Numerous studies have reported that m6A-related regulatory factors play pivotal roles in tumor development through diverse mechanisms. Moreover, recent studies have indicated the aberrant expression of multiple regulatory factors in OC. Therefore, this paper comprehensively reviews research advancements concerning m6A in OC, aiming to elucidate the regulatory mechanism of m6A-associated regulators on pivotal aspects, such as proliferation, invasion, metastasis, and drug resistance, in OC. Furthermore, it discusses the potential of m6A-associated regulators as early diagnostic markers and therapeutic targets, thus contributing to the diagnosis and treatment of OC.

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Section: Introductionsupporting

confidence: 73%

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer

Zhang,

Ling,

Zhou

et al. 2024

Cancer Control

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METTL14-mediated m6A mRNA modification of G6PD promotes lung adenocarcinoma

Wu,

Li,

et al. 2024

Cell Death Discov.

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METTL14 functions as an RNA methyltransferase involved in m6A modification, influencing mRNA biogenesis, decay, and translation processes. However, the specific mechanism by which METTL14 regulates glucose-6-phosphate dehydrogenase (G6PD) to promote the progression of lung adenocarcinoma (LUAD) is not well understood. Quantitative measurement and immunohistochemistry (IHC) analysis have demonstrated higher levels of m6A in LUAD tissues compared to adjacent normal tissues. Additionally, the expression of METTL14 was significantly increased in LUAD tissues. In LUAD cell lines, both METTL14 and m6A levels were elevated compared to normal human lung epithelial cells. Knockdown of METTL14 markedly reduced LUAD cell proliferation, migration, and invasion. Conversely, overexpression of METTL14, but not the mutant form, significantly enhanced these cellular processes in LUAD. In vivo studies using nude mice with subcutaneously transplanted LUAD cells demonstrated that stable METTL14 knockdown led to notably reduced tumor volume and weight, along with fewer Ki67-positive cells and lung metastatic sites. Importantly, METTL14 knockdown reduced glycolytic activity in LUAD cells. Through a combination of RNA sequencing and MeRIP-sequencing, we identified numerous altered genes and confirmed that IGF2BP2 enhances G6PD mRNA stability after METTL14-mediated m6A modification, thereby promoting tumor growth and metastasis. Moreover, LUAD patients with higher levels of G6PD had poorer overall survival (OS). In conclusion, our study indicates that METTL14 upregulates G6PD expression post-transcriptionally through an m6A-IGF2BP2-dependent mechanism, thereby stabilizing G6PD mRNA. These findings propose potential diagnostic biomarkers and effective targets for anti-metabolism therapy in LUAD.

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METTL Family in Health and Disease

He,

Hao,

Song

et al. 2024

Mol Biomed

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Transcription, RNA splicing, RNA translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, RNA modifications, and protein modifications, play a crucial role in regulating gene expression. The methyltransferase-like protein (METTL) family, a constituent of the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across the cell nucleus, cytoplasm, and mitochondria. Members of the METTL family, through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting processes such as DNA replication, transcription, and mRNA translation, to participate in the maintenance of normal function or promote disease development. This review primarily examines the involvement of the METTL family in normal cell differentiation, the maintenance of mitochondrial function, and its association with tumor formation, the nervous system, and cardiovascular diseases. Notably, the METTL family is intricately linked to cellular translation, particularly in its regulation of translation factors. Members represent important molecules in disease development processes and are associated with patient immunity and tolerance to radiotherapy and chemotherapy. Moreover, future research directions could include the development of drugs or antibodies targeting its structural domains, and utilizing nanomaterials to carry miRNA corresponding to METTL family mRNA. Additionally, the precise mechanisms underlying the interactions between the METTL family and cellular translation factors remain to be clarified.

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METTL14‑mediated RNA methylation in digestive system tumors

Cited by 4 publications

References 123 publications

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer

METTL14-mediated m6A mRNA modification of G6PD promotes lung adenocarcinoma

METTL Family in Health and Disease

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