BACKGROUND: The molecular mechanisms involved in small-cell lung cancer (SCLC) are largely unknown. Recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a critical role. OBJECTIVES: There is an urgent need for suitable molecular biomarkers for SCLC diagnosis and for assessing patient prognosis. MATERIAL AND METHODS: In this study, we used public databases to identify mRNA-like candidate lncRNAs. A multi-step computational approach was used to construct a functional SCLC lncRNAs-mediated competing with endogenous RNA (ceRNA) network (LMCN) by integrating genome-wide lncRNAs and mRNA expression profiles, miRNA-target interactions, functional analyses, and clinical survival analyses. RESULTS: The results revealed the significance of lncRNAs interactions with ceRNAs in SCLC, indicating that integration of expression profiles and alternative splicing could be used to identify biomarkers and the underlying pathological changes. The following genes: EPB41L4A-AS1, HOXA-AS2, XIST, DLEU2, FGD5-AS1, ALMS1-IT1, SNHG12, MIR17HG, MIR4720, and SCARNA10 in cluster, as well as shared alternative splicing events, were considered to be critical genes. CONCLUSIONS: Olfactory transduction and endocytosis were the top-enriched pathways in SCLC. The selected cluster, including critical genes, might also be a potential pathway of SCLC pathogenesis. As a result, this research provides the perspective information to explore the potential critical genes and its pathways in SCLC therapy.
BACKGROUND: The molecular mechanisms involved in small-cell lung cancer (SCLC) are largely unknown. Recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a critical role. OBJECTIVES: There is an urgent need for suitable molecular biomarkers for SCLC diagnosis and for assessing patient prognosis. MATERIAL AND METHODS: In this study, we used public databases to identify mRNA-like candidate lncRNAs. A multi-step computational approach was used to construct a functional SCLC lncRNAs-mediated competing with endogenous RNA (ceRNA) network (LMCN) by integrating genome-wide lncRNAs and mRNA expression profiles, miRNA-target interactions, functional analyses, and clinical survival analyses. RESULTS: The results revealed the significance of lncRNAs interactions with ceRNAs in SCLC, indicating that integration of expression profiles and alternative splicing could be used to identify biomarkers and the underlying pathological changes. The following genes: EPB41L4A-AS1, HOXA-AS2, XIST, DLEU2, FGD5-AS1, ALMS1-IT1, SNHG12, MIR17HG, MIR4720, and SCARNA10 in cluster, as well as shared alternative splicing events, were considered to be critical genes. CONCLUSIONS: Olfactory transduction and endocytosis were the top-enriched pathways in SCLC. The selected cluster, including critical genes, might also be a potential pathway of SCLC pathogenesis. As a result, this research provides the perspective information to explore the potential critical genes and its pathways in SCLC therapy.
Entities:
Keywords:
alternative splicing; critical genes; small-cell lung cancer (SCLC)
Authors: Daniel F Comiskey; Huiling He; Sandya Liyanarachchi; Mehek S Sheikh; Isabella V Hendrickson; Lianbo Yu; Pamela L Brock; Albert de la Chapelle Journal: Sci Rep Date: 2020-11-17 Impact factor: 4.379