AUTHOR=Wang Zhonglin , Ren Ziyuan , Li Rui , Ge Junpeng , Zhang Guoming , Xin Yaodong , Qu Yiqing 

TITLE=Multi-Omics Integrative Bioinformatics Analyses Reveal Long Non-coding RNA Modulates Genomic Integrity via Competing Endogenous RNA Mechanism and Serves as Novel Biomarkers for Overall Survival in Lung Adenocarcinoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.691540

DOI=10.3389/fcell.2021.691540

ISSN=2296-634X

ABSTRACT=<p>Long non-coding RNA (lncRNA) plays a crucial role in modulating genome instability, immune characteristics, and cancer progression, within which genome instability was identified as a critical regulator in tumorigenesis and tumor progression. However, the existing accounts fail to detail the regulatory role of genome instability in lung adenocarcinoma (LUAD). We explored the clinical value of genome instability-related lncRNA in LUAD with multi-omics bioinformatics analysis. We extracted the key genome instability-related and LUAD-related gene modules using weighted gene co-expression network analysis (WGCNA) and established a competing endogenous RNA (ceRNA) network using four lncRNAs (<italic>LINC01224</italic>, <italic>LINC00346</italic>, <italic>TRPM2-AS</italic>, and <italic>CASC9</italic>) and seven target mRNAs (<italic>CCNF</italic>, <italic>PKMYT1</italic>, <italic>GCH1</italic>, <italic>TK1</italic>, <italic>PSAT1</italic>, <italic>ADAM33</italic>, and <italic>DDX11</italic>). We found that <italic>LINC01224</italic> is primarily located in the cytoplasm and that <italic>LINC00346</italic> and <italic>TRPM2-AS</italic> are primarily located in the nucleus (<italic>CASC9</italic> unknown). We found that all 11 genes were positively related to tumor mutational burden and involve drug resistance, cancer stemness, and tumor microenvironment infiltration. Additionally, an eight-lncRNA genome instability-related lncRNA signature was established and validated, predicting the overall survival and immunotherapy outcomes in LUAD. To conclude, we discovered that sponging microRNA, genome instability-related lncRNA functions as ceRNA, modulating genomic integrity. This research provides clinical references for LUAD immunotherapy and prognosis and interprets a potential genome instability-related ceRNA regulatory network in which <italic>LINC01224-miR-485-5p</italic>/<italic>miR-29c-3p-CCNF</italic>-<italic>RRM2</italic> and <italic>LINC01224-miR485-5p-PKMYT1</italic>-<italic>CDK1</italic> axes were the most promising pathways. However, the potential mechanisms underlying our findings still need biological validation through <italic>in vitro</italic> and <italic>in vivo</italic> experiments.</p>