Hepatocellular carcinoma (HCC) ranks fourth in cancer-related mortality worldwide. N1-methyladenosine (m1A), a methylation modification on RNA, is gaining attention for its role across diverse biological processes. However, m1A-related regulatory genes expression, its relationship with clinical prognosis, and its role in HCC remain unclear. In this study, we utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to investigate alterations within 10 m1A-related regulatory genes and observed a high mutation frequency (23/363). Cox regression analysis and least absolute shrinkage and selection operator were used to explore the association between m1A-related regulatory genes expression and HCC patient survival and identified four regulators that were remarkably associated with HCC patient prognosis. Additionally, an independent cohort from International Cancer Genome Consortium was studied to validate our discoveries and found to be consistent with those in the TCGA dataset. In terms of mechanism, gene set enrichment analysis linked these four genes with various physiological roles in cell division, the MYC pathway, protein metabolism, and mitosis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that PI3K/Akt signaling pathway had potential relevance to m1A-related regulatory genes in HCC. These findings indicate that m1A-related regulatory genes may play crucial roles in regulating HCC progression and be exploited for diagnostic and prognostic purposes.

The objectives of this study were to identify specific long noncoding RNAs (lncRNAs) in laryngeal squamous cell carcinoma (LSCC) and to clarify the function of cisplatin and paclitaxel on the confirmed laryngeal cancer lncRNAs. Fifty-four pairs of laryngeal tumor and adjacent normal tissue were collected. Candidate lncRNAs were searched in authorized databases. The significant lncRNAs were identified and confirmed through high-output real-time PCR. Chemotherapy assay evaluated the influences of cisplatin and paclitaxel on the significant lncRNAs. Thirty-seven cancer-related candidate lncRNAs were selected. Three up-expressed and two down-expressed significant lncRNAs were identified and confirmed. The expressions of lncRNA CDKN2B-AS1, HOTAIR and MALAT1 were dramatically reduced with the increasing concentration of cisplatin and paclitaxel and also lengthening of the treatment duration. Cisplatin and paclitaxel have target function on significant lncRNAs in LSCC, which presents novel molecular targets to cure LSCC patients and also leads an orientation for developing new drugs.

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and the 5-year overall survival rate remains poor. Protein kinase, membrane associated tyrosine/threonine (PKMYT1) is overexpressed in several cancers and participate in tumor progression. However, the mechanism of PKMYT1 in ESCC is unclear.PurposeThe objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC.Patients and methods  We detected the expression of PKMYT1 in ESCC patients and analysed the correlation with overall survival time and disease-free survival time. Then we detected PKMYT1 expression in ESCC cell lines and immortalized human esophageal epithelial cell line. Down-regulated PKMYT1 was carried out in KYSE70 and KYSE450 cells to invetigate the mechanism of PKMYT1 in ESCC cells.ResultsPKMYT1 was up-regulated in tumor tissues and ESCC cell lines, and higher expression of PKMYT1 correlated with poorer overall survival in ESCC patients. Besides, in ESCC cell lines KYSE70 and KYSE450, knocking down PKMYT1 allowed more cells to skip G2/M checkpoint to complete mitosis, which promoted cell apoptosis, inhibited cell proliferation, and prevented the EMT phenotype in vitro. Meantime, we also observed that down-regulated PKMYT1 in ESCC cells suppressed AKT/mTOR signaling pathway. These results demonstrated PKMYT1 may act as an oncogene in ESCC.ConclusionPKMYT1 plays an crutial role in ESCC progression, downregulated PKMYT1 might inhibit the development of ESCC by AKT/mTOR signaling pathway, and might be a novel target in the treatment of ESCC.

Background Growing evidence indicates that methylation status is associated with the pathogenesis of numerous types of cancers. Among these, hepatocellular carcinoma (HCC) is a deadly disease threatening global human health. Although 5-methylcytosine (m5C) has been identified as an important regulatory modification, its distribution in solid tumors, including HCC, remains unclear. The present study aimed to explore the distribution of m5C in HCC. Materials and Methods Six pairs of human HCC tissues and adjacent non-tumor tissues were collected to analyze the transcriptome-wide m5C methylation of long non-coding RNA (lncRNA). RNA MeRIP-seq was performed to identify m5C peaks on lncRNA and differences in m5C distribution between HCC and adjacent tissues. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were explored to predict the possible roles of m5C. Results Using m5C peak sequencing, we observed that a sequence motif was necessary for m5C methylation in HCC lncRNA. Unsupervised hierarchical cluster analysis confirmed that lncRNA m5C methylation occurred more frequently in HCC than adjacent non-tumor tissues. RNA sequencing data demonstrated that more genes were up-regulated by methylation in HCC, while methylation down-regulated more genes in adjacent non-tumor tissues. GO and KEGG pathway analyses revealed that genes having a significant correlation with m5C sites in lncRNA were involved in HCC signaling pathways. Conclusion Our results revealed the substantially different amounts and distributions of m5C in HCC compared to adjacent non-tumor tissue. We further predicted the cellular functions in HCC that m5C may participate in to provide evidence implicating m5C lncRNA epigenetic regulation in the tumorigenesis and progression in HCC.

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