Identification of LINC02310 as an enhancer in lung adenocarcinoma and investigation of its regulatory network via compre

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RESEARCH ARTICLE

Identification of LINC02310 as an enhancer in lung adenocarcinoma and investigation of its regulatory network via comprehensive analyses Wenyuan Zhao1,2, Jun Wang1, Qingxi Luo1, Wei Peng1, Bin Li2, Lei Wang3, Chunfang Zhang1 and Chaojun Duan1,2,3,4*

Abstract  Background:  Lung adenocarcinoma (LADC) is a major subtype of non-small cell lung cancer and has one of the highest mortality rates. An increasing number of long non-coding RNAs (LncRNAs) were reported to be associated with the occurrence and progression of LADC. Thus, it is necessary and reasonable to find new prognostic biomarkers for LADC among LncRNAs. Methods:  Differential expression analysis, survival analysis, PCR experiments and clinical feature analysis were performed to screen out the LncRNA which was significantly related to LADC. Its role in LADC was verified by CCK-8 assay and colony. Furthermore, competing endogenous RNA (ceRNA) regulatory network construction, enrichment analysis and protein–protein interaction (PPI) network construction were performed to investigate the downstream regulatory network of the selected LncRNA. Results:  A total of 2431 differentially expressed LncRNAs (DELncRNAs) and 2227 differentially expressed mRNAs (DEmRNAs) were from The Cancer Genome Atlas database. Survival analysis results indicated that lnc-YARS2-5, lncNPR3-2 and LINC02310 were significantly related to overall survival. Their overexpression indicated poor prognostic. PCR experiments and clinical feature analysis suggested that LINC02310 was significantly correlated with TNM-stage and T-stage. CCK-8 assay and colony formation assay demonstrated that LINC02310 acted as an enhancer in LADC. In addition, 3 targeted miRNAs of LINC02310 and 414 downstream DEmRNAs were predicted. The downstream DEmRNAs were then enriched in 405 Gene Ontology terms and 11 Kyoto Encyclopedia of Genes and Genomes pathways, which revealed their potential functions and mechanisms. The PPI network showed the interactions among the downstream DEmRNAs. Conclusions:  This study verified LINC02310 as an enhancer in LADC and performed comprehensive analyses on its downstream regulatory network, which might benefit LADC prognoses and therapies. Keywords:  LADC, LncRNA, TCGA​, ceRNA regulatory network, PPI

*Correspondence: [email protected] 1 Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China Full list of author information is available at the end of the article

Background NSCLC is a major cause of cancer-derived death worldwide, accounting for 85% of all lung cancers [1]. It can be classified into four subtypes: Lung adenocarcinoma (LADC), lung large cell carcinoma (LCLC), lung squamous cell carcinoma (LSCC) and lung neuroendocrine tumor (Lung NET) [2]. LADC, as a major type of NSCLC, has one of the highest mortality rates. Although

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