Long non-coding RNA LINC01133 represses KLF2, P21 and E-cadherin transcription through binding with EZH2, LSD1 in non small cell lung cancer.

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In this study, we screened LINCO1133 as a new candidate lncRNA which promotes NSCLC development and progression, in two independent datasets (GSE18842 and GSE19804) from the Gene Expression Omnibus (GEO). LINC01133 is previously found to be over-expressed in lung squamous cell cancer (LSCC) and knockdown its expression inhibits LSCC cells invasion. However, its' molecular mechanism and downstream targets involving in regulation of cancer cells phenotype is not known. Here, we found that LINC01133 expression is up-regulated in NSCLC tissues, and its' over-expression is associated with patients poor prognosis and short survival time. LINC01133 knockdown decreased NSCLC cells proliferation, migration, invasion and induced cell cycle G1/S phase arrest and cell apoptosis. Mechanistic investigations showed that LINC01133 could interact with EZH2, LSD1 and recruit them to KLF2, P21 or E-cadherin promoter regions to repress their transcription. Furthermore, rescue experiments demonstrated that LINC01133 oncogenic function is partly through regulating KLF2. Lastly, we found that there was negative correlation between LINC01133 and KLF2, P21 or E-cadherin in NSCLC. Overall, our findings illuminate how LINC01133 over-expression confers an oncogenic function in NSCLC that may offer a novel therapy target in this disease.", "claims": [{"id": "claim-method", "statement": "DFS and OS rates were calculated by the Kaplan–Meier method with the log-rank test applied for comparison.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26840083", "locator": "sections[24] \"Statistical analysis\" paragraph 2", "quote": "DFS and OS rates were calculated by the Kaplan–Meier method with the log-rank test applied for comparison."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To investigate aberrant lncRNAs in NSCLC, we firstly analyzed the microarray data from GEO datasets and found that LINC01133 was the highest up-regulated lncRNA in GSE18842 dataset (Figure 1A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26840083", "locator": "sections[3] \"LINC01133 expression was up-regulated and correlated with poor prognosis of NSCLC\" paragraph 2", "quote": "To investigate aberrant lncRNAs in NSCLC, we firstly analyzed the microarray data from GEO datasets and found that LINC01133 was the highest up-regulated lncRNA in GSE18842 dataset (Figure 1A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26840083"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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