Integrated analysis of dosage effect lncRNAs in lung adenocarcinoma based on comprehensive network

Abstract

Accumulating evidences indicate that cancer-related lncRNAs occur frequent somatic copy number alternation (SCNA). Although individual SCNA lncRNAs have been implicated in tumor biology, their regulatory mechanism has not been assessed in a systematic way. In order to explore the expression characteristics and biological functions of SCNA lncRNAs in cancer, we built a computational framework based on lncRNA expression profiles, lncRNA copy numbers and dosage sensitivity score (DSS). First, we found that the lncRNAs with different DSS were involved in distinct biological processes, while those with the same DSS had similar functions. Second, some of the lncRNAs participated in the progression and metastasis of lung adenocarcinoma (LUAD) through cis-acting regulation. In lncRNA-TF-mRNA network, lncRNAs interacted with 4 TFs and affected the immune system, and further influenced LUAD progression. Third, competing endogenous RNA network analysis inferred that lncRNA ENSG00000240990 competed with HOXA10 to absorb hsa-let-7a/b/f/g-5p and affected patient prognosis in LUAD. Last but not least, by integrating target information of miRNA we also provided a new perspective for the discovery of potential small molecule drugs. In summary, we systematically analyzed the regulatory role of SCNA lncRNAs. This work may facilitate cancer research and serve as the basis for future efforts to understand the role of SCNA lncRNAs, develop novel biomarkers and improve knowledge of tumor biology.