Pan-cancer Characterization And Functional Analysis Of M~6A-related Long Non-coding RNAs

[Objective]As the most common modification of RNA in mammals,N6-methyladenosine(m~6A)plays an important role in the biological processes of RNA transcription,splicing,stability and translation.Long non-coding RNA(lnc RNA)is a class of non-coding RNA with a length of more than 200 nt,which can act as important targets of m~6A modification and play important roles in various regulations including chromatin modification and direct transcriptional regulation.The interaction of m~6A and lnc RNA plays a key role in the tumorigenesis and progression of tumors.However,a systematic research which comprehensively identify m~6A-related lnc RNA and analyze their functions at the pan-cancer level is still lacking.Here,we identified m~6A-related lnc RNA in human tumors through integrating pan-cancer transcriptome data and experimentally supported m~6A modification information.The function of m~6A-related lnc RNA was explored through the competitive endogenous RNA(ce RNA)network,drug sensitivity and survival analysis.[Methods]In this study,the Pearson correlation method was first used to identify the relationship between candidate lnc RNA and m~6A regulators by integrating the transcriptome data of 33 cancer types from TCGA and the m~6A modification site information from the m6A2Target and m6A-Atlas databases.Next,the m~6A-related lnc RNA-mediated ce RNA networks were constructed based on the mi RNA interactions which experimentally supported and transcriptome data.Then,the pharmacological treatment data related to cancer cell lines were downloaded from the GDSC database,and the relationship between m~6A-related lnc RNA and their drug sensitivities was explored by the theory of Gene Set Enrichment Analysis(GSEA).Finally,prognostic analysis was performed based on the median expression of m~6A-related lnc RNA to explore its impact on the prognosis of cancer patients.[Results]We identified 5,877 m~6A-related lnc RNA in 33 cancer types,and found that the m~6A modification of lnc RNA is common in pan-cancerlevel.In particularly,we found that a large number of lnc RNA were positively correlated with m~6A regulators.In addition,we identified 356 cancer-common and 744 cancer-specific m~6A-related lnc RNA at the pan-cancer level.The cancer-specific lnc RNA were associated with tissue specificity,and cancer-common lnc RNA were conserved in cancer-related biological functions.Based on the result of ce RNA network construction,drug sensitivity and survival analysis,we developed an integrated platform of m~6A-related lnc RNA,Lnc2m6A(http://hainmu-biobigdata.com/Lnc2m6A).Theresource provides multiple options for users to browse and search the relationship between lnc RNAs and m~6A modulators as well as the functions of lnc RNAs.By using this online tool,we found that lnc RNA FGD5-AS1 is associated with a great number of m~6A regulators.Moreover,the expression of this lnc RNA is associated with the drug resistance of cisplatin and shows great prognostic efficacy in breast cancer.In addition,the m~6A-related lnc RNA DANCR competes with multiple neurohumoral and developmental genes in low-grade gliomas.Meanwhile,it serves as a risk factor in the prognosis of LGG patients.[Conclusions]In conclusion,our work depicted the global landscape of m~6A-related lnc RNA in pan-cancer by integrating human cancer transcriptome data and m~6A modification data.The Lnc2m6A database,which embraced ce RNA,drug sensitivity,and survival analysis for m~6A-related lnc RNAs,can provide accurate epigenetic targets for tumor treatment.The completion of this project will benefit researchers to explore the function of m~6A-modified lnc RNA,and provide novel insights in understanding of epigenetic regulation and offer novel potential molecular therapeutic targets.