m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.

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“…In seminoma, YTHDF3 and VIRMA are significantly overexpressed and there is a positive correlation between their expression [95].…”

Section: Ythdf3mentioning

confidence: 96%

Functions of N6-methyladenosine and its role in cancer

et al. 2019

Mol Cancer

859

816

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“…As the best characterized as m6A "readers", YTH domain containing family 1 (YTHDF1) promotes translation efficiency by binding m6A-modified mRNA [29], whereas YTHDF2 decreases mRNA stability and facilitates mRNA degradation [30]. YTHDF3 facilitates translation and decay of m6A-modified mRNAs through cooperation with YTHDF1 and YTHDF2 [31]. Next, we further investigated whether LPS stimulation-promoted upregulation of GNAS mRNA is related to m6A modification.…”

Section: Lps-induced Il-6 Expressionmentioning

confidence: 99%

GNAS promotes inflammation-related hepatocellular carcinoma progression by promoting STAT3 activation

Ding

Zhang

et al. 2020

Cell Mol Biol Lett

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Background: Hepatocellular carcinoma (HCC) is still the most common cause of cancer-related mortality worldwide and accumulating studies report that HCC is frequently linked to chronic inflammation. G-protein alpha-subunit (GNAS)-activating mutations have recently been reported to form a rare subgroup of inflammatory liver tumors. In this study, we investigated the roles of GNAS in inflammation-related HCC progression and its underlying mechanism. Methods: Lipopolysaccharides (LPS) and diethylnitrosamine were employed to stimulate HCC cells to an induced inflammatory response. qRT-PCR, immunohistochemistry and immunoblotting were performed to detect the expression of GNAS in HCC tissues and cell lines. Expression levels of proinflammatory cytokines were detected by qRT-PCR and ELISA. N6-methyladenosine (m6A) methylation of GNAS mRNA was detected by RNAbinding protein immunoprecipitation (RIP). Transcription factors activation profiling plate array was performed to investigate the underlying mechanism in GNAS promoting interleukin-6 (IL-6) expression in HCC cells. HCC cell invasion was determined by transwell assay in vitro, and tumorigenesis was assessed with a subcutaneous xenograft mouse model of HCC. Results: We found that LPS stimulation promotes GNAS expression in HCC cells through increasing m6A methylation of GNAS mRNA. The high expression level of GNAS promotes LPS-induced HCC cell growth and invasion by interacting with signal transducer and activator of transcription 3 (STAT3). Furthermore, GNAS knockdown inhibits LPS induced-IL-6 expression in HCC cells by suppressing STAT3 activation. Moreover, we found that GNAS promotes LPS-induced STAT3 activation in HCC cells through inhibiting long non-coding RNA TPTEP1 interacting with STAT3. In addition, GNAS expression promotes HCC development in mice and is related to poor survival. Conclusions: Our findings for the first time indicate a tumor-promoting role of GNAS in inflammation-related HCC progression and provide a novel potential target for HCC therapy.

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“…Recent studies have found that METTL3 can regulate mRNA structure independently of its m6A catalytic activity, thus promoting oncogene translation [70] .KIAA1429 also given the name :virus , just similar to m6A methyltransferase related gene. It is reported that KIAA1429 promotes the multiplication , shift and invasion of liver cancer via modulating the mRNA methylation level where cell line was situated Id2 [30] .Also,A study expressed that KIAA1429 presented signi cant up-regulation in seminoma and down-regulation in the non-tumours [71] . KIAA1429, which features high expression on breast cancer , is able to enhance the multiplication and metastasis of breast cancer not only in vivo but also in vitro [72] .…”

Section: Discussmentioning

confidence: 94%

Effects Which M6A RNA Methylation Regulation Exerts on the Prognosis of Hepatocellular Carcinoma

B¹,

Pei²,

Sun³

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) ,which has been known as the most common subtype in the range of primary liver cancer . Besides, it hails as one of China ’s common cancers , giving rise to the major cancer death cause in men. N6 methyladenosine (m6A) RNA methylation is under the regulation of m6A RNA methylation regulators in dynamic way (the proteins of "writer" "eraser"; "reader"). More and more evidences show that the m6A modification level is connected with self-renewal of tumor stem cells, the growth, proliferation, anti chemotherapy and radiosensitivity of tumor cells. The relationship between m6A RNA and human cancer types has been confirmed in a variety of cancers. This research aims to investigate the relationship betwixt m6A RNA methylation regulators and liver cancer. Methods: firstly, the comparison of the expression levels harbored by 13 major m6A RNA methylation regulators in liver cancer with normal tissues was conducted by means of the data of TCGA database. Secondly, we cluster the presentation data of m6A RNA methylated regulator uniformly and dissect HCC tissue into two subgroups (group 1 and 2) by comparing these subgroups according to the overall survival rate (OS), WHO phase and pathological level . Thirdly, based on the combination of least absolute contraction with selection operator (lasso) regression, the risk characteristics of m6A RNA methylation regulators was constructed , which affected OS in TCGA analysis. Results: there were significant differences in the presentation degrades held by 12 major m6A RNA methylation regulators in liver cancers and normal tissues. The primary liver cancer was divided into 1 and 2 groups. It was found that the OS of 1 subgroup was poor, the WHO stage was high and the pathological grade was high. In TCGA analysis, five m6A methylation regulators (YTHDF1, ZC3H13, YTHDF2, METTL3 and KIAA1429) were selected to affect OS, and a risk marker significantly related to who staging was constructed, which was also an independent prognostic marker of OS. Conclusion: m6A RNA methylation regulator is a key player in the progression of HCC and has potential value in the prediction and treatment of HCC.

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m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance

Cited by 55 publications

References 65 publications

Functions of N6-methyladenosine and its role in cancer

Functions of N6-methyladenosine and its role in cancer

GNAS promotes inflammation-related hepatocellular carcinoma progression by promoting STAT3 activation

Effects Which M6A RNA Methylation Regulation Exerts on the Prognosis of Hepatocellular Carcinoma

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