Clear cell renal cell carcinoma(ccRCC)is a heterogeneous malignancy with poor prognosis.Methyla-tion of the N6 position of adenosine(m6A),the most common epigenetic modification in both messen-ger RNAs and noncoding RNAs,has been reported to regulate the initiation and progression of ccRCC.However,whether and how m6A-related long noncoding RNAs(m6ArlncRNAs)signify the progression of ccRCC remain unclear.We found m6ArlncRNAs are effective signatures illustrating immune landscape and risk stratification in ccRCC.We identified two differently expressed m6ArlncRNAs(DEm6ArlncRNAs),AC008870.2 and EMX2OS,as independent risk factors for overall survival of ccRCC patients,by apply-ing stringent variable selection procedure to data from the Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma project.The risk score generated from the DEm6ArlncRNA expression categorizes patients into either high or low-risk groups,between which,enrichment analysis indicated an enrichment in immune-related pathways.Under different DEm6ArlncRNA transcription pattern,the two risk groups differ in im-mune cell population composition and expression levels of therapy targeting genes.Nanoparticle is sat-isfactory strategy to delivering therapeutic drugs.For further clinical translation,we designed a novel nanoparticle delivery system packaged STM2457(STM@8P4 NPs),which selectively inhibits AC008870.2-correlated m6A writer.STM@8P4 NPs loaded drug successfully with uniform particle size,long-term sta-bility and high release efficiency.STM@8P4 NPs can easily enter ccRCC cells and showed a highly efficient ccRCC killing activity in vitro.Our results therefore indicate that m6ArlncRNAs expression can depict tu-mor microenvironment,predict prognosis for ccRCC patient and give hint to therapeutic strategies in ccRCC.

Ruixuan Chen;Ping Ouyang;Licong Su;Xi Xu;Penghu Lian;Yanqin Li;Qi Gao;Yifan Zhang;Sheng Nie;Fan Luo;Ruqi Xu;Xiaodong Zhang;Xiaoxi Li;Yue Cao;Peiyan Gao;Juanjuan Kang;Jun Wu;Lu Li

National Clinical Research Center for Kidney Disease,State Key Laboratory of Organ Failure Research,Guangdong Provincial Clinical Research Center for Kidney Disease,Nanfang Hospital,Southern Medical University,Guangzhou 510000,China;Department of Health Management,Nanfang Hospital,Southern Medical University,Guangzhou 510000,China;Department of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou 510000,China;Department of Urology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS&PUMC),Beijing 100730,China;Department of Urology,Nanfang Hospital,Southern Medical University,Guangzhou 510000,China;Affiliated Foshan Maternity&Child Healthcare Hospital,Southern Medical University,Foshan 528000,China;School of Biomedical Engineering,Sun Yat-sen University,Shenzhen 518107,China;Department of Radiation Oncology,Nanfang Hospital,Southern Medical University,Guangzhou 510000,China

中国化学快报（英文版）

[1]Ruixuan Chen;Ping Ouyang;Licong Su;Xi Xu;Penghu Lian;Yanqin Li;Qi Gao;Yifan Zhang;Sheng Nie;Fan Luo;Ruqi Xu;Xiaodong Zhang;Xiaoxi Li;Yue Cao;Peiyan Gao;Juanjuan Kang;Jun Wu;Lu Li-.Nanoparticles targeting at methylases with high correlation to N6-methyladenosine-related lncRNA signatures as potential therapy of kidney clear cell carcinoma)[J].中国化学快报（英文版）,2022(10):4610-4616

methylases,Methyla,messen,m6ArlncRNAs,DEm6ArlncRNAs,AC008870,EMX2OS,DEm6ArlncRNA,STM2457,8P4

Nanoparticles,targeting,correlation,N6,methyladenosine,signatures,potential,therapy,kidney,carcinoma,Clear,renal,ccRCC,heterogeneous,malignancy,poor,prognosis,most,common,epigenetic,modification,both,ger,noncoding,has,been,reported,regulate,initiation,progression,However,whether,long,signify,remain,unclear,We,found,are,effective,illustrating,immune,landscape,risk,stratification,identified,two,differently,expressed,independent,factors,overall,survival,patients,by,apply,stringent,variable,selection,procedure,data,from,Cancer,Genome,Atlas,Kidney,Renal,Cell,Carcinoma,project,score,generated,expression,categorizes,into,either,low,groups,between,which,enrichment,analysis,indicated,pathways,Under,transcription,pattern,population,composition,levels,genes,sat,isfactory,strategy,delivering,therapeutic,drugs,For,further,clinical,translation,designed,novel,nanoparticle,delivery,system,packaged,NPs,selectively,inhibits,correlated,writer,loaded,successfully,uniform,size,term,sta,bility,release,efficiency,can,easily,enter,cells,showed,highly,efficient,killing,activity,vitro,Our,results,therefore,that,depict,mor,microenvironment,predict,give,hint,strategies

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