Transcriptional machinery of TNF-α-inducible YTH domain containing 2 (YTHDC2) gene

Tanabe, Atsushi; Konno, Junpei; Tanikawa, Kenya; Sahara, Hiroeki

doi:10.1016/j.gene.2013.11.005

Cited by 47 publications

(47 citation statements)

References 32 publications

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“…Other studies have shown that the recognition of m 6 A by YTHDC2 is crucial for embryonic differentiation [17,18] . Furthermore, YTHDC2 may be a susceptibility gene for pancreatic cancer [19] and plays an important role in the development of liver cancer [20] . However, there has been little research into the relationship between YTHDC2 and CRC.…”

Section: Introductionmentioning

confidence: 99%

YTHDC2 Promotes the Apoptosis of Colorectal Cancer Cells Through the p38MAPK Signaling Pathway

Sun

et al. 2020

Preprint

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Background The role of the m6A-binding protein YTHDC2 in the occurrence and development of colorectal cancer (CRC) is unclear. We aimed to explore the molecular mechanisms underlying this process and clarify the signaling pathway involved. Methods Firstly, the relationship between YTHDC2 and CRC in TCGA database was analyzed to identify relevant signaling pathways and biological processes. Then, western blot was used to analyze expression of YTHDC2 in HCT116 and Caco2 cells. After knockdown or overexpression of YTHDC2 in the above cells, RT-PCR and western blot were used to analyze p38MAPK, p-p38MAPK, and downstream apoptosis-related proteins in the MAPK signaling pathway. Flow cytometry was performed to detect changes in apoptosis. Results And the results were shown that the expression of YTHDC2 was significantly lower in tumor tissues than in normal tissues. Increased expression of YTHDC2 was associated with better overall survival among patients with CRC. Gene set enrichment analysis revealed that YTHDC2 regulates the MAPK signaling pathway. Flow cytometry revealed apoptosis was significantly reduced and enhanced in response to YTHDC2 knockdown and overexpression, respectively. There was no significant change in the expression of p38MAPK, while p-p38MAPK was significantly increased in response to overexpression and decreased in response to knockdown. Gene Expression Profiling Interactive Analysis showed apoptotic protein expression to be positively correlated with YTHDC2 expression, consistent with the results of RT-PCR and western blot. Conclusion In general, apoptosis of CRC cells is promoted by YTHDC2 via activation of the exogenous death receptor and endogenous mitochondrial apoptosis-related pathways in the p38MAPK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

YTHDC2 Promotes the Apoptosis of Colorectal Cancer Cells Through the p38MAPK Signaling Pathway

Sun

et al. 2020

Preprint

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“…However, the function of YTHDC2 in the cancer cells and the mechanism by which the YTHDC2 gene is transcribed in these cells are largely unknown [29]. In a recent work, Tanabe et al showed that YTHDC2 plays an important role in cancer cell growth, the activation/recruitment of ATF-2 and c-Jun to the YTHDC2 promoter region is necessary for the transcription of YTHDC2, and that histone deacetylase activity is required for the efficient expression of YTHDC2 in both hepatocyte and hepatocellular carcinoma cells [29]. Furthermore, rare mutations in the YTHDC2 gene have been identified in individuals with autism spectrum disorders [30].…”

Section: Introductionmentioning

confidence: 99%

Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?

Fanale

Iovanna

Calvo

et al. 2014

Expert Opinion on Therapeutic Targets

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“…Several studies have pointed out that the occurrence of liver cancer is related to the abnormal expression of m 6 A RNA methylation modulators [20,25,[27][28][29][35][36][37]. Zhao et al [36] reported that increased YTHDF1 is related to poor prognosis of liver cancer patients, and YTHDF1 plays an important role in regulating liver cancer cell metabolism and cell cycle progression.…”

Section: Discussionmentioning

confidence: 99%

“…b-c Univariate and multivariate Cox regression analyses of the association between clinicopathological factors (including the risk score) and overall survival of patients in the ICGC dataset, the hazard ratios (HR), 95% confidence intervals increasing m 6 A modification of ID2 mRNA. Furthermore, Tanabe et al [37] reported that YTHDC2 plays an important role in the growth of liver cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

Qin

Zhang

et al. 2020

BMC Cancer

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Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators ("writer," "eraser," and "reader" proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

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Transcriptional machinery of TNF-α-inducible YTH domain containing 2 (YTHDC2) gene

Cited by 47 publications

References 32 publications

YTHDC2 Promotes the Apoptosis of Colorectal Cancer Cells Through the p38MAPK Signaling Pathway

YTHDC2 Promotes the Apoptosis of Colorectal Cancer Cells Through the p38MAPK Signaling Pathway

Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?

Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

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