Pan-cancer Analysis Reveals m^(6)A Variation and Cell-specific Regulatory Network in Different Cancer Types

As the most abundant messenger RNA(mRNA)modification,N^(6)-methyladenosine(m^(6) A)plays a crucial role in RNA fate,impacting cellular and physiological processes in various tumor types.However,our understanding of the role of the m^(6) A methylome in tumor heterogeneity remains limited.Herein,we collected and analyzed m^(6) A methylomes across nine human tissues from 97 m^(6) A sequencing(m^(6) A-seq)and RNA sequencing(RNA-seq)samples.Our findings demonstrate that m^(6) A exhibits different heterogeneity in most tumor tissues compared to normal tissues,which contributes to the diverse clinical outcomes in different cancer types.We also found that the cancer type-specific m^(6) A level regulated the expression of different cancer-related genes in distinct cancer types.Utilizing a novel and reliable method called“m^(6) A-express”,we predicted m^(6) A-regulated genes and revealed that cancer type-specific m^(6) A-regulated genes contributed to the prognosis,tumor origin,and infiltration level of immune cells in diverse patient populations.Furthermore,we identified cell-specific m^(6) A regulators that regulate cancer-specific m^(6) A and constructed a regulatory network.Experimental validation was performed,confirming that the cell-specific m^(6) A regulator CAPRIN1 controls the m^(6) A level of TP53.Overall,our work reveals the clinical relevance of m^(6) A in various tumor tissues and explains how such heterogeneity is established.These results further suggest the potential of m^(6) A in cancer precision medicine for patients with different cancer types.

Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine

In 2003,severe acute respiratory syndrome coronavirus（SARS-CoV）emerged in Guangdong Province,China,infected more than 8000 individuals,and resulted in a 10%mortality rate（Rota et al.2003）.Later,in 2012,a novel CoV,Middle East respiratory syndrome coronavirus（MERS-CoV）,was isolated from the sputum of a man in Saudi Arabia（Perl et al.2014）.Notably,MERS-CoV recently reemerged in the Republic of Korea, and killed 36 out of 186 confirmed cases （Korea Centers for Disease Control and Prevention 2015）. Therefore, SARS-CoV still carries the potential for resurgence; efforts are being made to prevent the recurrence of an epidemic.

Piperlongumine Inhibits Zika Virus Replication In vitro and Promotes Up-Regulation of HO-1 Expression, Suggesting An Implication of Oxidative Stress

Owing to the widespread distribution of mosquitoes capable of transmitting Zika virus, lack of clinical vaccines and treatments, and poor immunity of populations to new infectious diseases, Zika virus has become a global public health concern. Recent studies have found that Zika virus can continuously infect human brain microvascular endothelial cells.These cells are the primary components of the blood–brain barrier of the cerebral cortex, and further infection of brain tissue may cause severe damage such as encephalitis and fetal pituitary disease. The present study found that a biologically active base, piperlongumine(PL), inhibited Zika virus replication in human brain microvascular endothelial cells, Vero cells, and human umbilical vein endothelial cells. PL also significantly increased heme oxygenase-1(HO-1) gene expression, while silencing HO-1 expression and using the reactive oxygen species scavenger, N-acetylcysteine, attenuated the inhibitory effect of PL on Zika virus replication. These results suggest that PL induces oxidative stress in cells by increasing reactive oxygen species. This, in turn, induces an increase in HO-1 expression, thereby inhibiting Zika virus replication. These findings provide novel clues for drug research on the prevention and treatment of Zika virus.

Pitfalls of restriction enzyme analysis in identifying, characterizing,typing, and naming viral pathogens in the era of whole genome data, as illustrated by HAdV type 55

Restriction endonuclease analysis(REA),or restriction fragment length polymorphism(RFLP),was useful for identifying and determining the relatedness and putative identities of microbial strains(Tang et al.,1997)and for characterizing and discriminating large numbers of samples inexpensively in the past。

Systematic analysis of clinical relevance and molecular characterization of m^(6)A in COVID-19 patients

N6-methyladenosine(m6A)is the most prevalent post-transcriptional RNA modification in mRNA and long non-coding RNAs of eukaryotes,and its biological functions are mediated by m6A writers,erasers and readers.1 A nuclear methyltransferase complex consisting of METTL3,METTL14,WTAP,VIRMA,ZC3H13,RBM15(or RBM15B),YWHAG,TRA2A and CAPRIN1 catalyzes the m6A modifications,acting as m6A writers.1 m6A demethylase ALKBH5 as well as m6A demethylase FTO mediate the demethylation of m6As,acting as the m6A erasers.

Specific Regulation of m^(6)A by SRSF7 Promotes the Progression of Glioblastoma

Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m^(6)A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m^(6)A methylation.We then indicate that SRSF7 is a novel m^(6)A regulator,which specifically facilitates the m^(6)A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase complex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m^(6)A methyltransferase.The two m^(6)A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m^(6)A and validates the presence and functional importance of temporal-and spatial-specific regulation of m^(6)A mediated by RNA-binding proteins(RBPs).

Development of functional antibodies against influenza B virus by activation-induced cytidine deaminase in hybridoma cells

Dear Editor,Influenza B viruses(IBVs)have circulated among humans for more than 80 years.Seasonal influenza virus epidemics caused by two IBV lines(Victoria and Yamagata)and influenza A virus have considerable effects on public health globally and result in approximately290,000–650,000 annual influenza-attributed deaths(Caini et al.,2015;Pan et al.,2015).Currently,the most effective countermeasures against influenza B virus infections are influenza virus vaccines(Subbarao and Matsuoka,2013).However,these vaccines have limited efficacy because only strain-matched humoral immune responses are induced.