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.

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.

Liver cancer is the fifth most common malignant tumor in terms of incidence and the third leading cause of cancer-related mortality globally. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Although great progress has been made in surgical techniques, hepatic artery chemoembolization, molecular targeting and immunotherapy, the prognosis of liver cancer patients remains very poor. N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells and regulates various stages of the RNA life cycle. Many studies have reported that the abnormal expression of m6A-related regulators in HCC represent diagnostic and prognostic markers and potential therapeutic targets. In this review, firstly, we introduce the latest research on m6A-related regulators in detail. Next, we summarize the mechanism of each regulator in the pathogenesis and progression of HCC. Finally, we summarize the potential diagnostic, prognostic and therapeutic value of the regulators currently reported in HCC.

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.

N6-methyladenosine (m6a)-related mRNAs and lncRNAs have been explored for their functions in several cancers. The present study aimed to identify potential signatures of m6a-related lncRNAs in hepatocellular carcinoma (HCC). We downloaded the expression and clinical data from The Cancer Genome Atlas (TCGA) database. The interacted mRNAs and lncRNAs, prognosis-related lncRNAs, potential metabolic pathways of lncRNAs, immune infiltration of various cells, and CD274 (PD-L1) -related lncRNAs were analyzed. Then, in vitro experiments explored the role of AC012073.1 (LOC105377626) in HCC cell lines. We found that candidate 14 lncRNA signatures play functions in HCC maybe by affecting immune infiltration, cell cycle, Notch signaling pathway, etc. LncRNA AC012073.1 (LOC105377626) functions as oncogenic roles in affecting HCC prognosis.

Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1), tumor necrosis factor receptor superfamily member 9 (4-1BB), and B-cell lymphoma-extra large (Bcl-xL) in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG) patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM) patients, and 28 gastric carcinoma (Ca) patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P < 0.05 compared with CG). There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P < 0.05). Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P < 0.05). Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue.

N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. The dynamic and reversible m6A modification of RNA plays a critical role in the occurrence and progression of tumors by regulating RNA metabolism, including translocation, mRNA stability or decay, pre-mRNA splicing, and lncRNA processing. Numerous studies have shown that m6A modification is involved in the development of various cancers. This review aims to summarize the significant role of m6A modification in the proliferation and tumorigenesis of CRC, as well as the potential of modulating m6A modification for tumor treatment. These findings may offer new therapeutic strategies for clinical implementation of m6A modification in CRC in the near future.

Cytotoxin-associated gene A (CagA) is one of the most important virulence factors of Helicobacter pylori, and serves a role in H. pylori-mediated tumorigenesis in gastric cancer. However, the underlying molecular mechanism remains to be elucidated. The present study aimed to investigate the effects of CagA on the proliferation and apoptosis of GES-1 cells, and the underlying mechanism. A CagA eukaryotic expression plasmid was constructed and transfected into GES-1 cells. The mRNA and protein levels of CagA, tumor necrosis factor receptor-associated factor 1 (TRAF1) and tumor necrosis factor receptor superfamily member 9 (4–1BB) were determined using the reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Western blot and ELISA analysis was used to detect the release of interleukin (IL)-8. An MTT assay and flow cytometric analysis was used to assess cell viability and apoptosis, respectively. Ectopic expression of CagA markedly increased TRAF1 and 4-1BB mRNA and protein levels in GES-1 cells. CagA increased the expression and release of IL-8 in GES-1 cells. The expression of CagA significantly promoted the proliferation (P<0.05) and inhibited the apoptosis (P<0.05) of GES-1 cells. In conclusion, CagA upregulated TRAF1/4-1BB, thereby promoting the proliferation and inhibiting the apoptosis of GES-1 cells.