The m6A methylation landscape stratifies hepatocellular carcinoma into 3 subtypes with distinct metabolic characteristics

Objective:Epigenetic aberration plays an important role in the development and progression of hepatocellular carcinoma(HCC).However,the alteration of RNA N6-methyladenosine(m6A)modifications and its role in HCC progression remain unclear.We therefore aimed to provide evidence using bioinformatics analysis.Methods:We comprehensively analyzed the m6A regulator modification patterns of 605 HCC samples and correlated them with metabolic alteration characteristics.We elucidated 390 gene-based m6A-related signatures and defined an m6Ascore to quantify m6A modifications.We then assessed their values for predicting prognoses and therapeutic responses in HCC patients.Results:We identified 3 distinct m6A modification patterns in HCC,and each pattern had distinct metabolic characteristics.The evaluation of m6A modification patterns using m6Ascores could predict the prognoses,tumor stages,and responses to sorafenib treatments of HCC patients.A nomogram based on m6Ascores showed high accuracy in predicting the overall survival of patients.The area under the receiver operating characteristic curve of predictions of 1,3,and 5-year overall survivals were 0.71,0.69,and 0.70 in the training cohort,and in the test cohort it was 0.74,0.75,and 0.71,respectively.M6Acluster C1,which corresponded to hypoactive mRNA methylation,lower expression of m6A regulators,and a lower m6Ascore,was characterized by metabolic hyperactivity,lower tumor stage,better prognosis,and lower response to sorafenib treatment.In contrast,m6Acluster C3 was distinct in its hyperactive mRNA methylations,higher expression of m6A regulators,and higher m6Ascores,and was characterized by hypoactive metabolism,advanced tumor stage,poorer prognosis,and a better response to sorafenib.The m6Acluster,C2,was intermediate between C1 and C3.Conclusions:HCCs harbored distinct m6A regulator modification patterns that contributed to the metabolic heterogeneity and diversity of HCC.Development of m6A gene signatures and the m6Ascore provides a more comprehensive understanding of m6A modifications in HCC,and helps predict the prognosis and treatment response.

The long non-coding RNA expression profile of Coxsackievirus A16 infected RD cells identified by RNA-seq

Coxsackievirus A16(CVA16) is one of major pathogens of hand, foot and mouth disease(HFMD) in children. Long non-coding RNAs(Inc RNAs) have been implicated in various biological processes,but they have not been associated with CVA16 infection. In this study, we comprehensively characterized the landscape of Inc RNAs of normal and CVA16 infected rhabdomyosarcoma(RD)cells using RNA-Seq to investigate the functional relevance of Inc RNAs. We showed that a total of 760 Inc RNAs were upregulated and 1210 Inc RNAs were downregulated. Out of these dysregulated Inc RNAs, 43.64% were intergenic, 22.31% were sense, 15.89% were intronic, 8.67% were bidirectional, 5.59% were antisense, 3.85% were s RNA host Inc RNAs and 0.05% were enhancer. Six dysregulated Inc RNAs were validated by quantitative PCR assays and the secondary structures of these Inc RNAs were projected. Moreover, we conducted a bioinformatics analysis of an Inc RNAs(ENST00000602478) to elucidate the diversity of modification and functions of Inc RNAs. In summary, the current study compared the dysregulated Inc RNAs profile upon CVA16 challenge and illustrated the intricate relationship between coding and Inc RNAs transcripts. These results may not only provide a complete picture of transcription in CVA16 infected cells but also provide novel molecular targets for treatments of HFMD.

Identification of micro RNAs in six solanaceous plants and their potential link with phosphate and mycorrhizal signalings

To date, only a limited number of solanaceous miRNAs have been deposited in the miRNA database. Here,Rgenome-wide bioinformatic identification of miRNAs was performed in six solanaceous plants（potato, tomato, tobacco,eggplant, pepper, and petunia）. A total of 2,239 miRNAs were identified following a range of criteria, of which 982 were from potato, 496 from tomato, 655 from tobacco, 46 from eggplant,45 were from pepper, and 15 from petunia. The sizes of miRNA families and miRNA precursor length differ in all the species.Accordingly, 620 targets were predicted, which could be functionally classified as transcription factors, metabolic enzymes, RNA and protein processing proteins, and other proteins for plant growth and development. We also showed evidence for miRNA clusters and sense and antisense miR NAs.Additionally, five Pi starvation- and one arbuscular mycorrhiza（AM）-related cis-elements were found widely distributed in the putative promoter regions of the miRNA genes. Selected miRNAs were classified into three groups based on the presence or absence of P1BS and MYCScis-elements, and their expression in response to Pi starvation and AM symbiosis was validated by quantitative reverse transcription-polymerase chain reaction（qRT-PCR）. These results show that conserved miRNAs exist in solanaceous species and they might play pivotal roles in plant growth, development, and stress responses.