The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

Chen, Mengnuo; Wong, Chun–Ming

doi:10.1186/s12943-020-01172-y

Cited by 244 publications

(209 citation statements)

References 102 publications

Supporting

Mentioning

193

Contrasting

Order By: Relevance

“…Moreover, high expression of HNRNPA2B1 and low expression of ALKBH5 were indicated as the risk factor for the survival of ESCA, and the combination of these two factors showed more predictive potential than the alone, although the ROC curve did not show robust prediction within 4 and 5 years, which because of that there are too few patients in the fourth and fifth years, which may lead to the instability of the ROC curve. It is reported that HNRNPA2B1 could selectively bind to m 6 A-containing transcripts via the “m 6 A-switch,” a mechanism in which m 6 A weakens Watson–Crick base pairing to destabilize the RNA hairpin structure and thereby exposes the single stranded hnRNP binding motif ( 37 ). HNRNPA2B1 has been reported to be a RNA-binding protein involved in different cancer progression ( 38 – 40 ).…”

Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

N6-methyladenosine (m 6 A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m 6 A modification and m 6 A RNA methylation regulators were involved in cancer progression. However, the m 6 A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m 6 A regulators using The Cancer Genome Atlas data and found 14 of 19 m 6 A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m 6 A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m 6 A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m 6 A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

show abstract

Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…6-8 m 6 A modification is installed by methyltransferases (termed as "m 6 A writers"), removed by demethylases (termed as "m 6 A erasers") and recognized by binding proteins (termed as "m 6 A readers"). 9,10 One class of direct and robust m 6 A readers are proteins containing the YTH domain, including YTHDF1-3 and YTHDC1-2. 11,12 Figure 1 YTHDC2 is downregulated in NSCLC tissues and cell lines.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of m⁶A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

et al. 2020

View full text Add to dashboard Cite

Background m 6 A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m 6 A reader, is associated with multiple cancers; however, little is known of its role in non‐small cell lung cancer (NSCLC). Methods The GEPIA, Oncomine and GEO databases were analyzed to assess expression of YTHDC2 in NSCLC patients. Quantitative polymerase chain reaction, western blot and immunohistochemistry were used to detect YTHDC2 expression in different NSCLC cell lines (H1299, H460, H292 and A549) and patients. The effects of YTHDC2 on NSCLC cell lines (A549 and H1299) proliferation and migration were employed using CCK8 and transwell assays. The potential target RNAs of YTHDC2 were obtained from the POSTAR database. Functional enrichment analysis of YTHDC2 targeted RNAs was performed using the Metascape database. Results GEPIA, Oncomine and GEO databases showed low expression of YTHDC2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. YTHDC2 expression was significantly decreased in different NSCLC cell lines and our clinical samples. Moreover, low expression of YTHDC2 was significantly associated with poor differentiation, lymph node metastasis, tumor size and stage. In addition, YTHDC2 could suppress the proliferation and migration ability of A549 and H1299 cell lines. Kaplan‐Meier Plotter database analysis revealed that patients with low level of YTHDC2 had a significantly poor prognosis. Finally, functional enrichment analysis of YTHDC2 targeted RNAs indicated several enriched pathways related to cancer. Conclusions These findings elucidate that YTHDC2 suppresses tumorigenesis in NSCLC, indicating that YTHDC2 may be a promising therapeutic target for NSCLC. Key points Significant findings of the study This study demonstrated that the downregulation of YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer (NSCLC). What this study adds YTHDC2 might be a promising therapeutic target for non‐small cell lung cancer (NSCLC).

show abstract

“…The occurrence and development of HCC involve interactions between genetics, epigenetics, and transcriptomic alterations (Aravalli et al, 2013). Epigenetic dysregulation promotes the initiation and progression of HCC (Chen and Wong, 2020).…”

Section: Introductionmentioning

confidence: 99%

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Cao

Luo

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: 5-methylcytosine (5mC) has been reported in the prognosis of a variety of cancers, however, its role in hepatocellular carcinoma (HCC) has not been investigated yet. This study aimed at identifying the molecular subtypes associated with 5mC and establishing a relevant score to predict its prognosis in HCC. Methods: Somatic gene mutation data and gene expression data were retrieved from The Cancer Genome Atlas database. Molecular subtypes were identified by unsupervised clustering based on the expression of 5mC regulators, and the molecular features of each subtype were investigated by survival, mutation, gene set variation, and immune cell infiltration analyses. Next, we performed a differentially expressed analysis based on the new subtypes and selected the overlapping genes for further analysis. We undertook univariate Cox analysis to analyze these genes and constructed a prognostic model by lasso regression analysis. Meanwhile, survival and gene set enrichment analyses were used to explore the prognosis and the relevant pathways, respectively. The LIRI cohort from the International Cancer Genome Consortium database was used as a reference to validate the 5mC subtypes and 5mC score. Results: Twenty-one types of 5mC regulators were employed in this study, and three 5mC-associated molecular subtypes were identified. These three subtypes presented significant differences in prognosis, immune cell infiltration, immune checkpoint inhibitors, signaling pathways, and mutational features. Compared with cluster 3, cluster 2 exhibited significantly increased expression of PD-L1, TIM3, Galectin9, CTLA4, and CD80, while PD-L1, TIM3, and CD80 were higher in cluster 2 than in cluster 1. Furthermore, a 5mC-related score, composed of seven genes (SGPP2, SALL4, B3GNT7, ROR1, MYBL2, SLC7A1, and CAND2), was proven to be significantly associated with prognosis. The established subtypes and scores were thus successfully verified by the validated cohort.

show abstract

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

Cited by 244 publications

References 102 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Downregulation of m⁶A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Contact Info

Product

Resources

About

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

Cited by 244 publications

References 102 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Downregulation of m6A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Contact Info

Product

Resources

About

Downregulation of m⁶A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer