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Q. Wang
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P2.15 - SCLC/Neuroendocrine Tumors (ID 716)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.15-009 - Linc00173 Modulates Chemoresistance of Small Cell Lung Cancer by Functioning as a Competing Endogenous RNA to Regulate Etk Expression (ID 8971)
09:30 - 09:30 | Author(s): Q. Wang
- Abstract
Background:
Small cell lung cancer (SCLC) that constitutes of 15-18% of all lung cancers is a highly lethal malignancy. The functional effects of long noncoding RNAs(lncRNAs) in cancer have been widely recognized. Long intergenic non-protein coding RNA 173(Linc00173) was first identified in SCLC, and was found to be involved in chemoresistance. We aimed to explore the regulatory mechanisms of Linc00173 using drug-resistant cell lines and human tissues.
Method:
We used microarrays to compare expression profiles of lncRNAs in SCLC cell line and the drug-resistant subline and Linc00173 was identified. Linc00173 was examined in 60 SCLC patient samples by qRT-PCR assay. The functional roles of Linc00173 in SCLC were studied by overexpression and RNA interference approaches in vitro and in vivo. The localization of the genes were involved in competitive endogenous RNAs(ceRNAs) regulatory network was studied by separating cytoplasmic and nuclear RNA fractions from SCLC. Bioinformatic analysis, luciferase assays, RNA immunoprecipitation and pull-down assays were performed to elucidate the role of Linc00173 in mechanism of ceRNA. The positive Linc00173/Etk correlation was further verified by qRT-PCR assay and bivariate correlation analysis in clinical tissues and blood samples.
Result:
We found that Linc00173 expression was significantly associated with chemoresistance and the shorter survival time in SCLC patients. Downregulation of Linc00173 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs, while upregulation of Linc00173 promoted the proliferation and induced multidrug resistance both in vitro and in vivo. Linc00173 overexpression enhanced the expression of Etk through competitively ‘spongeing’ miRNA-218 resulting in the activation of STAT3. Particularly, the ceRNA regulatory network of above genes was occurred in nucleus. Finally, the positive Linc00173/Etk correlation was found in SCLC tissues and blood samples.
Conclusion:
Figure 1Linc00173 was first identified to promote proliferation and chemoresistance of SCLC. It regulates levels of Etk by acting as ‘sponger ’of miR-218. These genes may be novel indices for clinical diagnosis of tumor growth and chemoresistance in SCLC.
