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Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression

Abstract

The functional effects of long noncoding RNAs (lncRNAs) in cancer have been widely recognized. However, there is little research on SCLC-related lncRNAs. Here, long intergenic nonprotein coding RNA 173 (Linc00173) was first shown to be involved in chemoresistance and progression of small-cell lung cancer (SCLC). We found that Linc00173 was highly expressed in SCLC chemoresistant cell lines, and promoted SCLC cells chemoresistance, proliferation, and migration-invasion. Animal studies validated that Linc00173 induced tumor chemoresistance and growth of SCLC in vivo. Moreover, Linc00173 upregulated Etk through functioning as a competitive endogenous RNA (ceRNA) by “sponging” miRNA-218 and led to the upregulation of GSKIP and NDRG1, resulting in the translocation of β-catenin. Importantly, expression analysis revealed that both Linc00173 and Etk were upregulated in SCLC patient samples and exhibiting positive Linc00173/Etk correlation. High expression of Linc00173 closely correlated with chemoresistance, extensive stage, and shorter survival in SCLC patients. Collectively, our study illustrated a Linc00173-mediated process that facilitated chemoresistance and progression in SCLC, which might provide treatment strategy against SCLC.

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Acknowledgements

The SCLC Human SCLC cell lines NCI-H82, H209 were obtained as a generous gift from Dr Ji Lin of MD Anderson Cancer Center. The flow cytometry analysis was supported by Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University.

Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81572244, 81602631, and 81772458); Natural Science Foundation of Guangdong Province (key) (2015A030311028); The Clinical Research Initiative Project of Southern Medical University (LC2016ZD029); Major Basic Research Projects and Major Applied Research Projects of Educational Commission of Guangdong Province (2017KZDXM015).

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GL, ZW, and ZF conceived and designed the experiments. ZF, WQ, WS, HW, and GY performed the experiments. ZF, WQ, WS, HW, and LS analyzed the data. ZF, WQ, WS, LS, PJ, and LM wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Weiliang Zhu or Linlang Guo.

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The authors declare that they have no conflict of interest.

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Zeng, F., Wang, Q., Wang, S. et al. Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression. Oncogene 39, 293–307 (2020). https://doi.org/10.1038/s41388-019-0984-2

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