Alteration of N6-Methyladenosine RNA Profiles in Cisplatin-Induced Acute Kidney Injury in Mice.
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ABSTRACT:
SUBMITTER: Li CM
PROVIDER: S-EPMC8299335 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:N6-methyladenosine (m6A) modification is the most universal and abundant post-transcriptional modification of eukaryotic RNA and occurs mainly at the consensus motif RR (m6A) CH (R = A or G, H = A, C, or U) in long internal exons, near stop codons, or in the 3' untranslated region (UTR). "Writers," "erasers," and "readers" are responsible for the occurrence, removal, and recognition of m6A modification, respectively. Substantial evidence has shown that m6A RNA modification can exert important functions in physiological and pathological processes. Cardiovascular diseases (CVDs) are a wide array of disorders affecting heart or vessels, including atherosclerosis (AS), hypertension (HT), ischemia/reperfusion (I/R) injury, myocardial infarction (MI), stroke, cardiac hypertrophy, heart failure (HF), and so on. Despite the advances in lipid-lowering drugs, antihypertensives, antiplatelet agents, and anticoagulation therapy, CVDs are still the leading cause of death worldwide. Recent studies have suggested that m6A modification of RNA may contribute to the pathogenesis of CVDs, providing a novel research insight for CVDs. Herein, we provide an up-of-date summarization of the molecular mechanism of m6A and the roles of m6A in different types of CVDs. At last, we propose that m6A might be a potiential biomarker or therapeutic target for CVDs.
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Project description:We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m?A), in particular, has attracted the interest of researchers all around the world. m?A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation. m?A is installed by "writers", removed by "erasers", and recognized by "readers"; thus, it can be compared to the reversible and dynamic epigenetic modifications in histones and DNA. Given its fundamental role in determining the way mRNAs are expressed, it comes as no surprise that alterations to m?A modifications have a deep impact in cell differentiation, normal development and human diseases. Here, we review the proteins involved in m?A modification in mammals, m?A role in gene expression and its contribution to cancer development. In particular, we will focus on acute myeloid leukaemia (AML), which provides an initial indication of how alteration in m?A modification can disrupt normal cellular differentiation and lead to cancer.
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Project description:BackgroundArecoline is known as the main active carcinogen found in areca nut extract that drives the pathological progression of oral squamous cell carcinoma (OSCC). Studies have revealed that dysregulation of RNA N6-methyladenosine (m6A) methyltransferase components is intimately linked to cancer initiation and progression, including oral cancer.MethodsThe arecoline-induced dysregulated methyltransferase-like 3 (METTL3) gene was identified using RNA-seq transcriptome assay. Using in vitro and in vivo models, the biological roles of METTL3 in arecoline-transformed oral cancer were examined.ResultsWe found that METTL3 was markedly elevated in arecoline-exposed OSCC cell lines and OSCC tissues of areca nut chewers. We identified that hypoxia-inducible factor 1-alpha (HIF-1α) stimulated METTL3 expression at the transcriptional level and further proved that METTL3-MYC-HIF-1α formed a positive autoregulation loop in arecoline-transformed OSCC cells. Subsequently, we manifested that METTL3 depletion profoundly reduced cell proliferation, cell migration, oncogenicity, and cisplatin resistance of arecoline-exposed OSCC cells.ConclusionsDeveloping novel strategies to target METTL3 may be a potential way to treat OSCC patients, particularly those with areca nut chewing history and receiving cisplatin treatment.
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