Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential

Fan, Yongfei; Li, Xinwei; Sun, Huihui; Gao, Zhaojia; Zhu, Zheng; Yuan, Kai

doi:10.3390/biom12091224

Cited by 23 publications

(12 citation statements)

References 161 publications

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“…While PODXL is known to be another specific podocyte marker, we believe that its correlation with NPHS2 in multiple glomerular diseases is new. Even if S100A6 is expressed in other cell types (23), we also determined that it correlated very highly and very specifically with NPHS2 only. We identified 3 transcripts, IGFBP5, SLC9A3R2, and ENG that correlated with all 3 of the GEC markers (Table 3).…”

Section: Jcimentioning

confidence: 77%

The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease

Clair,

Soloyan,

Cravedi

et al. 2024

JCI Insight

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Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle–dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.

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Section: Jcimentioning

confidence: 77%

The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease

Clair,

Soloyan,

Cravedi

et al. 2024

JCI Insight

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“…The high expression of WTAP is significantly associated with poor prognosis in gastric cancer patients 31 . Besides, WTAP acts as a tumor suppressor gene by methylating 3'-UTR of CAV-1 and then activating NF-κB signaling pathway in endometrial cancer 32 . But there have been no reports about the role of WTAP in CC.…”

Section: Discussionmentioning

confidence: 99%

PIWI-interacting RNA-17458 is oncogenic and a potential therapeutic target in cervical cancer

Liu,

Li,

et al. 2023

J. Cancer

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Cervical cancer (CC) is one of the leading cancers among the female reproductive system. The piwi-interacting RNA (piRNA) function and biogenesis has been studied in various cancers, including CC. But the precise mechanism of piRNA in CC is still unknown. In our study, we found that piRNA-17458 was overexpressed in CC tissues and cells. piRNA-17458 mimic and inhibitor promoted and suppressed proliferation, migration and invasion ability of CC cells, respectively. We also demonstrated that piRNA-17458 mimic could contribute to tumor growth in mice xenograft models. Besides, we also found that the piRNA-17458 mimic could enhance mRNA N6-methyladenosine(m6A) levels and increase WTAP stability in CC cells, while the effects of the mimic was reversed by the WTAP knockdown. The results of dual luciferase reporter assay showed that WTAP was a direct target of piRNA-17458. Knockdown of WTAP attenuated proliferation, migration and invasion of CC cells in piRNA-17458 mimic group. Our finding not only demonstrates for the first time that piRNA-17458 is overexpressed in CC tissues and cells, but also shows that piRNA-17458 promotes tumorigenesis of CC in a WTAP-mediated m6A methylation manner.

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“…1 ), activating and enhancing METTL3 activity and promoting the recognition of RNA substrates, and thus enhancing MTC methylation efficiency ( 25 , 26 ). By contrast, WTAP is essential for promoting the enrichment of METTL3, METTL14 and other methyltransferases, transporting MTC into the nucleus and stabilizing MTC activity in the organism ( 27 , 28 ). VIRMA and ZC3H13 are relatively newly discovered m6A methyltransferases.…”

Section: The M6a Key Enzyme In the Development Of Crcmentioning

confidence: 99%

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review)

Shao,

Han,

Huang

et al. 2023

Int J Oncol

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RNA methylation modifications are closely linked to tumor development, migration, invasion and responses to various therapies. Recent studies have shown notable advancements regarding the roles of RNA methylation in tumor immunotherapy, the tumor microenvironment and metabolic reprogramming. However, research on the association between tumor chemoresistance and N6-methyladenosine (m6A) methyltransferases in specific cancer types is still scarce. Colorectal cancer (CRC) is among the most common gastrointestinal cancers worldwide. Conventional chemotherapy remains the predominant treatment modality for CRC and chemotherapy resistance is the primary cause of treatment failure. The expression levels of m6A methyltransferases, including methyltransferase-like 3 (METTL3), METTL14 and METTL16, in CRC tissue samples are associated with patients' clinical outcomes and chemotherapy efficacy. Natural pharmaceutical ingredients, such as quercetin, have the potential to act as METTL3 inhibitors to combat chemotherapy resistance in patients with CRC. The present review discussed the various roles of different types of key RNA methylation enzymes in the development of CRC, focusing on the mechanisms associated with chemotherapy resistance. The progress in the development of certain inhibitors is also listed. The potential of using natural remedies to develop antitumor medications that target m6A methylation is also outlined.

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Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential

Cited by 23 publications

References 161 publications

The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease

The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease

PIWI-interacting RNA-17458 is oncogenic and a potential therapeutic target in cervical cancer

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review)

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