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LncRNA SLC16A1-AS1 as a novel prognostic biomarker in non-small cell lung cancer.

ABSTRACT: Long non-coding RNAs (lncRNAs) have proved to act as crucial biomarkers in tumors. Novel biomarkers in non-small cell lung cancer (NSCLC) need to be investigated badly. To identify the differentially expressed lncRNAs between NSCLC tissue and adjacent tissue, microarray analysis was performed. lncRNA SLC16A1-AS1 was significantly less expressed in NSCLC tissue than that in adjacent tissue. Gain-of-function experiments was performed to determine the biological functions of SLC16A1-AS. In situhybridization and survival analysis were applied in lung cancer tissue samples to determine the prognostic role of SLC16A1-AS1. It was showed that SLC16A1-AS1 was remarkably downregulated in NSCLC tissues and cell lines. Functionally, SLC16A1-AS1 overexpression could inhibit the viability and proliferation of lung cancer cell, block the cell cycle and promote cell apoptosis in vitro which may result from reduced phosphorylation of rat sarcoma (RAS)/ proto-oncogene serine/threonine-protein kinase (RAF)/ mitogen-activated protein kinase kinase (MEK)/ extracellular regulated protein kinases (ERK) pathway caused by elevated expression of SLC16A1-AS1. Clinical sample analysis showed that SLC16A1-AS1 had a favorable impact on the overall survival and progression-free survival of patients with NSCLC. Our results suggested that SLC16A1-AS1 may act as a potential biomarker for patients with NSCLC.

SUBMITTER: Liu HY

PROVIDER: S-EPMC6996107 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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lncRNA SLC16A1-AS1 as a novel prognostic biomarker in non-small cell lung cancer.

Liu Hong Yue HY Lu Sheng Rong SR Guo Zi Han ZH Zhang Zhi Sheng ZS Ye Xuan X Du Qiong Q Li Huan H Wu Qiang Q Yu Bo B Zhai Qing Q Liu Jin Long JL

Journal of investigative medicine : the official publication of the American Federation for Clinical Research 20190731 1

Long non-coding RNAs (lncRNAs) have proved to act as crucial biomarkers in tumors. Novel biomarkers in non-small cell lung cancer (NSCLC) need to be investigated badly. To identify the differentially expressed lncRNAs between NSCLC tissue and adjacent tissue, microarray analysis was performed. lncRNA SLC16A1-AS1 was significantly less expressed in NSCLC tissue than that in adjacent tissue. Gain-of-function experiments was performed to determine the biological functions of SLC16A1-AS. In situhybr ...[more]

PMID: 31371390

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Project description:BackgroundNon-small-cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC.MethodsWe assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4-knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analyses. The significance of autophagy-related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4-mediated autophagic cell death in NSCLC.ResultsRBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy-related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3-MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell-injected nude mice, elevating autophagy-related protein levels and inducing apoptosis and necrosis in tumor tissues.ConclusionIn NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.

Dataset Information

LncRNA SLC16A1-AS1 as a novel prognostic biomarker in non-small cell lung cancer.

Publications

lncRNA SLC16A1-AS1 as a novel prognostic biomarker in non-small cell lung cancer.

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