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Tumor Inhibitory Effect of Long Non-coding RNA LOC100505817 on Gastric Cancer.

ABSTRACT: Gastric cancer (GC) is one of the major malignancies worldwide. Emerging evidence has revealed the potential involvement of long noncoding RNA (lncRNA) in human genetic disorders and cancer, but the role of LOC100505817 remains unknown. Thus, in this study, we isolated tissues from GC patients to characterize the functional importance of LOC100505817 in GC tumorigenesis. We also proposed a hypothesis that the regulation of Wnt/β-catenin pathway by LOC100505817 was regulated by miR-20a-mediated WT1. After the collection of cancer tissues and adjacent tissues were obtained from GC patients, expression of LOC100505817, Wnt/β-catenin pathway- and EMT-related genes was quantified. Ectopic expression and knockdown experiments were applied in order to investigate the protective role of LOC100505817 in the progression of GC. Subsequently, cell viability, flow cytometry for apoptosis and cell cycle were detected via CCK-8, while migration and invasion were determined using scratch test and Transwell assay respectively. Then interactions among LOC100505817, miR-20a and WT1 were explored by dual luciferase reporter gene assay, RNA pull down assay and RNA binding protein immunoprecipitation (RIP) assay. The results found poor expression LOC100505817 was poorly expressed in GC cells and tissues. Overexpressed LOC100505817 resulted in the significant reduction of cell proliferation, migration and invasion as well as the expression of Wnt2b, β-catenin, CyclinD1, N-cadherin, Vimentin and snail, while increased cell apoptosis along with the expression of E-cadherin. Wnt/β-catenin pathway and EMT in GC cells were suppressed by LOC100505817 through miR-20a-inhibted WT1. In summary, our results provided evidence suggesting that LOC100505817 inhibits GC through LOC100505817-mediated inhibition of Wnt/β-catenin pathway, that leads to the overall restraining of GC cell proliferation, migration and invasion through miR-20a-reduced WT1.

SUBMITTER: Zheng L

PROVIDER: S-EPMC8354317 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in 'biological regulation', 'metabolic process', 'cell communication', 'developmental process', 'cell proliferation', 'reproduction' and the 'cell cycle'. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.

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Tumor Inhibitory Effect of Long Non-coding RNA LOC100505817 on Gastric Cancer.

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