The biological function of m6A methyltransferase KIAA1429 and its role in human disease

Zhang, Xiaoyu; Li, Meng jiao; Lei, Xia; Zhang, Hairong

doi:10.7717/peerj.14334

Cited by 19 publications

(13 citation statements)

References 81 publications

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“…Our findings demonstrated that KIAA1429 contributed to OSCC tumorigenesis by inducing m6A methylation of INHBA in OSCC cell lines. KIAA1429, an m6A methyltransferase, plays a tumorigenic role in multiple cancers by mediating m6A modification of mRNA, lncRNA, and circRNA 21 . KIAA1429 is upregulated and plays an oncogenic role in both breast and gastric cancer 31,32 .…”

Section: Discussionmentioning

confidence: 99%

Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated m6A modification

Chen,

Fan

2024

J Oral Pathology Medicine

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BackgroundInhibin A and N6‐methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6‐methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene “Inhibin A” that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6‐methyladenosine methyltransferase KIAA1429‐mediated N6‐methyladenosine methylation modification.MethodsBioinformatics analysis and quantitative real‐time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit‐8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation‐qPCR, quantitative real‐time polymerase chain reaction, and Western blotting experiments.ResultsInhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6‐methyladenosine level of Inhibin A in oral squamous cell carcinoma.ConclusionsInhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated N6‐methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.

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Section: Discussionmentioning

confidence: 99%

Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated m6A modification

Chen,

Fan

2024

J Oral Pathology Medicine

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“…VIRMA has been primarily investigated in the context of cancer and has been reported as an oncogenic factor in various cancer types, including breast cancer 18,19 . However, the specific molecular mechanisms underlying its oncogenic role vary significantly, involving both m 6 A-dependent and m 6 A-independent pathways.…”

Section: Discussionmentioning

confidence: 99%

VIRMA-mediated m6A modification is essential for active ribosome biogenesis

Zhou,

Wu,

et al. 2023

Preprint

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N6-methyladenosine (m6A) modification plays crucial roles in tissue development and homeostasis. However, the mechanisms underlying cellular adaptation of m6A modification and their impact on protein synthesis machinery remain unclear. VIRMA, the largest and evolutionarily conserved core of the m6A methyltransferase complex, is highly expressed in the embryonic brain and various cancers. Here, we demonstrate that VIRMA-mediated m6A modification is essential for active ribosome biogenesis. VIRMA depletion destabilizes the entire writer complex and reduces m6A levels, leading to decreased proliferation and increased apoptosis of neural progenitor/stem cells (NPCs), ultimately causing severe forebrain developmental defects. Mechanistically, VIRMA depletion impairs ribosome biogenesis by inhibiting mRNA decay, triggering a P53-dependent ribosomal stress response and compromising global protein synthesis. Importantly, these findings extend to human cancer cells, suggesting the conservation of this mechanism. Overall, our study reveals the critical role of m6A in adapting protein synthesis machinery during brain development and in cancer.

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“…The m6A writer complex includes the catalytic methyltransferase like 3 (METTL3) which forms a stable complex with methyltransferase like 14 (METTL14) forming the m6A-METTL Complex (MAC) in which METTL3 transfer the methyl group from S-adenosyl methionine (SAM) to the adenosine residue within the RRACH consensus motif in RNA [ 62 , 63 ]. In addition to the MAC, the m6A writer complex includes regulatory subunits, i.e., Wilms’ tumor 1 (WT1)-associating protein (WTAP) [ 64 ], Vir like m6A methyltransferase associated (VIRMA) [ 65 , 66 , 67 ], RNA binding motif protein 15 (RBM15) [ 68 ], RNA binding motif protein 15B (RBM15B) [ 68 , 69 ], and zinc finger CCCH-type containing 13 (ZC3H13) [ 70 ]. These proteins interact with MAC and modulate its activity and/or target specificity [ 71 , 72 , 73 ].…”

Section: N6-methyladenosine (M6a)mentioning

confidence: 99%

Changes in m6A in Steatotic Liver Disease

Petri,

Cave,

Klinge

2023

Genes

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Fatty liver disease is one of the major causes of morbidity and mortality worldwide. Fatty liver includes non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), now replaced by a consensus group as metabolic dysfunction-associated steatotic liver disease (MASLD). While excess nutrition and obesity are major contributors to fatty liver, the underlying mechanisms remain largely unknown and therapeutic interventions are limited. Reversible chemical modifications in RNA are newly recognized critical regulators controlling post-transcriptional gene expression. Among these modifications, N6-methyladenosine (m6A) is the most abundant and regulates transcript abundance in fatty liver disease. Modulation of m6A by readers, writers, and erasers (RWE) impacts mRNA processing, translation, nuclear export, localization, and degradation. While many studies focus on m6A RWE expression in human liver pathologies, limitations of technology and bioinformatic methods to detect m6A present challenges in understanding the epitranscriptomic mechanisms driving fatty liver disease progression. In this review, we summarize the RWE of m6A and current methods of detecting m6A in specific genes associated with fatty liver disease.

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The biological function of m6A methyltransferase KIAA1429 and its role in human disease

Cited by 19 publications

References 81 publications

Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated m6A modification

Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated m6A modification

VIRMA-mediated m6A modification is essential for active ribosome biogenesis

Changes in m6A in Steatotic Liver Disease

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