NSUN2-mediated mRNA m^(5)C Modification Regulates the Progression of Hepatocellular Carcinoma

RNA modifications affect many biological processes and physiological diseases.The 5-methylcytosine(m^(5)C)modification regulates the progression of multiple tumors.However,its characteristics and functions in hepatocellular carcinoma(HCC)remain largely unknown.Here,we found that HCC tissues had a higher m^(5)C methylation level than the adjacent normal tissues.Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways,such as the Ras and PI3K-Akt pathways.The m^(5)C methyltransferase NSUN2 was highly expressed in HCC tissues.Interestingly,the expression of many genes was positively correlated with the expression of NSUN2,including GRB2,RNF115,AATF,ADAM15,RTN3,and HDGF.Real-time PCR assays further revealed that the expression of the mRNAs of GRB2,RNF115,and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells.Furthermore,NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway.Moreover,knocking down NSUN2 caused cell cycle arrest.Taken together,our study demonstrates the vital role of NSUN2 in the progression of HCC.

RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells

Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment.However,the mechanisms that control the resistance of EGFR-TKIs remain largely unknown.RNA structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain unclear.Here,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of NSCLC.Our results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to EGFR-TKIs.RNA structure formation in YRDC 30 UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and protein.Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.

5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer

Non-small-cell lung cancer （NSCLC）, the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymetbylcytosine （ShmC） signatures in circulating cell-free DNA （cfDNA） that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminat- ing tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identi- fied six potential biomarkers from 66 patients and 67 healthy controls （mean decrease accuracy 〉 3.2, P 〈 3.68E-19） using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient＇s cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.

An Imported Confirmed Case of COVID-19 Vaccinated in Brazil——Shanghai Municipality,China,March 17,2021

On March 17,2021,a 42-year-old male returning from Brazil tested positive by Qingpu CDC for coronavirus disease 2019(COVID-19)during medical observation at a designated isolation point.He was then sent to the Shanghai Public Health Clinical Center(SHPHCC)and confirmed again,and because he demonstrated no abnormal clinical signs(until the infection was controlled),he was diagnosed as an asymptomatic infection.