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̬ʾΰ񻯵ĹؼmicroRNA

680 Ķ 2020-6-8 16:57 |˷:paper|ϵͳ:Ľ| , Ϣ, ҽѧͳ, DZRNA, ֢

ΰȫΧ방֢صҪԭ򡣷ٰ֮һΰȣΪԡ֢оеһ̱ʽǷDZRNAãDZRNAȷΪ°Ӻӡڰ֢չУDZRNAϸڻγɲɷָRNAˮƽͳһ壬ͬRNA֮Ķ̬໥ú;Ҫá

ǿһֶķת¼ˮƽؽٰݻ׶RNA໥硣ʾ˾˫ֽṹȻͬ磬ҷÿ׶ζӰĹؼRNAӡ˸ȫĻݷܣṩ˸֢̽Ƶĸ繤ߣһΪоΰ־DZҩеṩ

գعѷPLoS Computational Biology, 16(5): e1007793. (2020)

https://doi.org/10.1371/journal.pcbi.1007793


ܣ

Abstract

Non-coding RNAs are fundamental to the competing endogenous RNA (CeRNA) hypothesis in oncology. Previous work focused on static CeRNA networks. We construct and analyze CeRNA networks for four sequential stages of lung adenocarcinoma (LUAD) based on multi-omics data of long non-coding RNAs (lncRNAs), microRNAs and mRNAs. We find that the networks possess a two-level bipartite structure: common competing endogenous network (CCEN) composed of an invariant set of microRNAs over all the stages and stagedependent, unique competing endogenous networks (UCENs). A systematic enrichment analysis of the pathways of the mRNAs in CCEN reveals that they are strongly associated with cancer development. We also find that the microRNA-linked mRNAs from UCENs have a higher enrichment efficiency. A key finding is six microRNAs from CCEN that impact patient survival at all stages, and four microRNAs that affect the survival from a specific stage. The ten microRNAs can then serve as potential biomarkers and prognostic tools for LUAD.


ݣ

DZRNANon-coding   RNA, ncRNAٷ֢񻯵ĴжӲɻȱáЩRNA   ѧԴԾRNA Competing   endogenous RNA, CeRNA˵Ļɲ֡ü˵Ϊ̽ͬͰ֢Ļƺݻṩ˸оӽǡ֮ǰĹҪھ̬CeRNA   硣֢ķչУDZڵCeRNA   ѱֲ䣬оCeRNA   Ķ̬仯

ٰLung   adenocarcinoma, LUADΪһоԭͰLUAD   ĸ˳ݻͣڳDZRNA   Long   non-coding RNAs, lncRNAs΢RNA microRNA, miRNAʹRNA messenger   RNA, mRNAѧݣͨRNA   IJ컯ڼԭƥmicroRNA   ĿꡢԮCeRNA   ˵ѡȡRNA   ֮ĸطĸ͵CeRNA   硣ǷmicroRNAs   mRNAs   lncRNAsɣ˫ͼṹTwo-level   bipartite structure

ȽLUAD microRNA   ֣CeRNA   ȻΪ磺ȫһ鲻microRNA   ɵĹеԴԾ磨The   common competing endogenous networks, CCENsԼͬеmicroRNA ɵĶеԴԾ磨The   unique competing endogenous networks, UCENsCeRNA mRNA ϵͳĻ Gene ontology, GO;ٿȫ飨Kyoto   encyclopedia of genes and genomes, KEGGͨ·ĸֹCeRNA 방 ֢ݻصͨ·أLUAD ͵Ķ방֢س̶Ҳӽܡ⣬UCENs   microRNA   ӵmRNAs   ڴCCENs    UCENs ֱѡȡmRNAs иߵĸЧʡ


 ˵

1. ڰ֢Ļѧݣӱݴ裬LUAD ˳ݻCeRNA硣TCGAݿlncRNAmicroRNAmRNAߵĻݣʹò컯miRNA Ŀƥ䡢ԼCeRNA裬˰֢ĸ˳ӦRNAɵCeRNA硣

ͼ


2. Ϊ֤ĿɿԣͳRNAģFCֵRNAеƽĸ͵LUADmRNAGOBiological processKEGG Pathwayͨ򸻼Чʷо˲ͬ방֢ĿGOͨKEGGԡ


    򸻼Чʷ


3. CeRAN˵CeRNA绮Ϊ硱(UCEN)͡硱(CCEN)ӽоCeRNAβ֮Ĺϵ

CeRNAͼ


4. ϲٴݣʹK-M߷оCeRNAеRNAڵжԲӰ졣



K-M߷


ԣ

1. ڻѧݵ罨ģѰҼ־ǶⰩ֢ķûƣϢѧֶν֤оһĿɿԡΪһʺ̽뼲֮ϵ춨

2. RNA໥˫ͼṹĽڵܹӰ착֢񻯹ͨصķܹõ⼲ݻɺѰDZڵҩе㡣

Ӧüֵ

ϵͳؽ˼صĻ̺繹IJ裬ͨԴڵͳƷϢصĵݿ֤ѰҰ֢־ΪĿǰҩƺ;׼ҽָDZڵķΪٴӦṩָܵ

Ϊݽģṩ˼·䷽ҲӦڸӹ㷺ݷͻݵģ͹ܹչӦ÷ΧԼϵͳ۶ѧӰ죬ٽѧƵĿٷչ塣


չ

ѧϢѧأ

1. ܷ絰ʡת¼ӣTFȣϽУ

2. ̽ѰCeRNAصķΰͶ񻯵ݻǷͬڣ

3. ʵ֤еõӰLUAD˵ķӱ־ʵǷڣ̽εùϵ

4. ϽЩٷչĵϸоβ֯񻯹Уϸ͵ĸıԼͬϸڲ໥氩֢񻯹̵ݻɣ

أ

5. Ӧøָ㷨ѰһձڵĹ뼲֮Ĺ

Կѧأ 

6. fMRIȾɫӫǡ΢缫е\Ľһչһ֯٣ԣ֣󡢹ӬӺȣϸڽз໥о



˶ʿĹ

оڼ֢صķDZRNA໥о漰硢ϢҽѧͳƵȡ

׳. ʾΰ־[D]. ݣݴѧѧ뼼ѧԺ2020.


ѡԴ壺

֢ҪĹȫ֮һҷΰڰ֢ռߡΰУСϸռ85%ٰLUADǷСϸҪٰ͡ԭ԰֢ĻϢӶڴӷӻƽǶо֢ķͷչDZRNA໥ãķҪĻػ֮һ㷺Ĵڸ֯ٵϸʱձģʽСһͨķչоԱϷָijDZRNA΢RNA״RNAȣ˽⵽DZRNAͨת¼ˮƽĻڰҪáǵĹнԴԾRNA˵RNAӼ໥磬RNAӻоLUAD氩֢񻯵ݻɡ


CeRNAоݣ

DZRNANon-coding RNA, ncRNAٷ֢񻯵ĴжӲɻȱáЩRNA ѧԴԾRNACompeting endogenous RNA, CeRNA˵Ļɲ֡ü˵Ϊ̽ͬͰ֢Ļƺݻṩ˸оӽǡ֮ǰĹҪھ̬CeRNA 磬оCeRNA Ķ̬仯ٰLung adenocarcinoma, LUADΪһоԭͰLUAD ĸ˳ݻͣڳDZRNALong non-coding RNAs, lncRNAs΢RNA microRNA, miRNAʹRNA messenger RNA, mRNAѧݣͨRNA IJ컯ڼԭƥmicroRNA ĿꡢԮCeRNA ˵ѡȡRNA ֮ĸطĸ͵CeRNA 硣

ǷmicroRNAs mRNAs lncRNAsɣ˫ͼṹTwo-level bipartitestructureȽLUAD microRNA ֣CeRNA ȻΪ磺ȫһ鲻microRNA ɵĹеԴԾ磨The common competing endogenous networks, CCENsԼͬеmicroRNA ɵĶеԴԾ磨The unique competing endogenous networks, UCENsCeRNA mRNA ϵͳĻ壨Gene ontology, GO;ٿȫ飨Kyoto encyclopedia of genes and genomes, KEGGͨ·ĸֹCeRNA 방֢ݻصͨ·أLUAD ͵Ķ방֢س̶Ҳӽܡ⣬UCENs microRNA ӵmRNAs ڴCCENs UCENs ֱѡȡmRNAs иߵĸЧʡ

ɷַPCA, principal component analysisо컯LUAD ݣCox ȱջعģͷɷּ䱾ʸԲӰ졣ͨPCA ıʸвξ࣬ǷһЩCeRNA 繤бmicroRNA ܹӰLUAD Kaplan-Meier ߷CCENmicroRNA ӰLUAD ȫĸmicroRNA ܹӰLUAD ijһضʮmicroRNA ΪϺͼLUAD DZڱ־ԤֶΡ


PCA㷨

Ƕھ컯LUAD һڡڡsample-RNA ݣʹPCA 㷨нάѧݵĹģѰҼ־оӰ졣Cox ȱջعȷPCA عݶӰ죬ԱԱָ꣬Ӷ֤PCA㷨ڽάȵͬʱҲһ̶ϱԭʼݵϢ⣬ͨPCA ɷֶӦıʸвξԼʸRNA LUAD FC ֵԣ̽ЩRNA PCA عݹжάԭʼϢҪáPCA㷨Cox ȱջعΪCeRNA 繤ݴʽIJ䣬ԼΪѰҿܵ־ṩݽάھ


CeRNAоPCA㷨Ĺϵ

һ棬PCA ȥ̻߸ͨѧݲɼе̶ܴϽԭʼsample-RNA ݵάȣͬʱҲһѧ壬ԲӰԱָꡣ

һ棬CeRNA ķͨѡȡmicroRNA ĿɸѡRNA ֮为ӣѧ壬̶ܴ˻ڲ방֢ݻķDZRNA ֮໥á



ϵͳʶ缰仯ɵҪۻŴʱϢıը罻ͨȺռѧϢɼڶʵݣͶݴͷشսĿǰо죬ԽԽоҲӦõӹ㷺ѧΧϢѧݴͷDZRNA໥ڵ罨ģصоݡ

һڼٴݺͻݣDZRNA֮໥õ硣

ڶΪͬݻ׶Σо񻯹Ӧ仯

ϢѧķĿɿԽ֤֤еһЩڵܹӰ첡˵

ģͨɷַݽнάϷջعȲ֤ۡ

֮һϵͳؽ˼صĻ̺繹IJ裬ͨԴڵͳƷϢصĵݿ֤Ϊһʺ̽뼲֮ϵ춨

֮߷ֹķDZRNA໥˫ͼṹĽڵܹӰ켲񻯹в˵ͨķܹõѰҼDZҩе㡣

֮ΧѰҼ־ΪĿ꣬ͨûѧݵ罨ģһϵе̽Ϣѧн֤оһĿɿԣкǿʵüֵ

ʱظһѧ·չһݴͷĿܣΪڻݽģṩ˼·䷽ҲӦڸӹ㷺ݷģ͹ܹչӦ÷ΧԼϵͳ۶ѧӰ죬ٽѧƵĿٷչ塣



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