VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer

Barros‐Silva, Daniela; Lobo, João; Guimarães‐Teixeira, Catarina; Carneiro, Isa; Oliveira, Jorge; Martens‐Uzunova, Elena S.; Henrique, Rui; Jerónimo, Carmen

doi:10.3390/cancers12040771

Cited by 68 publications

(59 citation statements)

References 54 publications

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“…METTL3 promotes development, progression and metastasis of PRAD through regulating MYC methylation, hedgehog pathway, and Wnt pathway (Cai et al, 2019;Ma et al, 2020;Yuan et al, 2020) and enhances bone metastasis through m 6 A-HuR-dependent mechanism (Li et al, 2020). VIRMA sustains invasiveness of PC cell through regulating oncogenic lncRNAs (Barros-Silva et al, 2020). YTHDF2 promotes the proliferation and migration of PC that is suppressed by miR-493-3p (Li et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

Liu

et al. 2020

Front. Genet.

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RNA methylation accounts for over 60% of all RNA modifications, and N6-methyladenosine (m6A) is the most common modification on mRNA and lncRNA of human beings. It has been found that m6A modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The m6A modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of m6A RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 m6A RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of p < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed m6A RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of m6A RNA methylation regulators in prostate cancer and determined a m6A gene expression classifier that well predicted the prognosis of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

Liu

et al. 2020

Front. Genet.

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“…Besides, METTL3 and VIRMA were also reported promoting the development and progression of PRC in different manners. [150][151][152][153] Renal Cell Carcinoma. METTL3 and METTL14 can not only promote the proliferation and metastasis of tumor cells, but also inhibit the progress of tumor.…”

Section: Review Llmentioning

confidence: 99%

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

Shi

Dai

et al. 2020

The Innovation

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N 6 -Methyladenosine (m 6 A) RNA modification brings a new dawn for RNA modification researches in recent years. This posttranscriptional RNA modification is dynamic and reversible, and is regulated by methylases (“writers”), demethylases (“erasers”), and proteins that preferentially recognize m 6 A modifications (“readers”). The change of RNA m 6 A modification regulates RNA metabolism in eucaryon, including translation, splicing, exporting, decay, and processing. Thereby the dysregulation of m 6 A may lead to tumorigenesis and progression. Given the tumorigenic role of abnormal m 6 A expression, m 6 A regulators may function as potential clinical therapeutic targets for cancers. In this review, we emphasize on the underlying mechanisms of m 6 A modifications in tumorigenesis and further introduce the potential m 6 A regulators-associated therapeutic targets for tumor therapy.

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“…The knockout of VIRMA triggers a compensatory feedback loop that enhances the expression of the catalytic METTL3 subunit. However, compensatory METTL3 overexpression is insufficient to maintain MTC function without VIRMA (Barros-Silva et al, 2020) (Fig. 3).…”

Section: Prostate Cancermentioning

confidence: 99%

Role of methyltransferase-like enzyme 3 and methyltransferase-like enzyme 14 in urological cancers

Tao

Zhao

Chen

2020

PeerJ

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N6-methyladenosine (m6A) modifications can be found in eukaryotic messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA). Several studies have demonstrated a close relationship between m6A modifications and cancer cells. Methyltransferase-like enzyme 3 (METTL3) and methyltransferase-like enzyme 14 (METTL14) are two major enzymes involved in m6A modifications that play vital roles in various cancers. However, the roles and regulatory mechanisms of METTL3 and METTL14 in urological cancers are largely unknown. In this review, we summarize the current research results for METTL3 and METTL14 and identify potential pathways involving these enzymes in kidney, bladder, prostate, and testicular cancer. We found that METTL3 and METTL14 have different expression patterns in four types of urological cancers. METTL3 is highly expressed in bladder and prostate cancer and plays an oncogenic role on cancer cells; however, its expression and role are opposite in kidney cancer. METTL14 is expressed at low levels in kidney and bladder cancer, where it has a tumor suppressive role. Low METTL3 or METTL14 expression in cancer cells negatively regulates cell growth-related pathways (e.g., mTOR, EMT, and P2XR6) but positively regulates cell death-related pathways (e.g., P53, PTEN, and Notch1). When METTL3 is highly expressed, it positively regulates the NF-kB and SHH-GL1pathways but negatively regulates PTEN. These results suggest that although METTL3 and METTL14 have different expression levels and regulatory mechanisms in urological cancers, they control cancer cell fate via cell growth- and cell death-related pathways. These findings suggest that m6A modification may be a potential new therapeutic target in urological cancer.

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VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer

Cited by 68 publications

References 54 publications

The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

Role of methyltransferase-like enzyme 3 and methyltransferase-like enzyme 14 in urological cancers

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