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Knockdown of lncRNA HIF1A-AS2 increases drug sensitivity of SCLC cells in association with autophagy

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Abstract

The aim of this study was to determine the effect of lncRNA HIF1A-AS2 on autophagy-associated drug resistance in small cell lung cancer (SCLC) cells. The expression of HIF1A-AS2 was silenced by siRNA in doxorubicin-sensitive H69 and doxorubicin-resistant H69AR cells. Then, cytotoxicity, apoptosis and autophagy analyses were carried out in the normoxic and CoCl2-induced hypoxic environment. The effect of HIF1A-AS2 on the expression levels of genes, which are associated with drug resistance and autophagy, was determinated by qRT-PCR analysis. The levels of MRP1, HIF-1α and Beclin-1 were analyzed by western blot method. Knockdown of HIF1A-AS2 increased doxorubicin sensitivity of SCLC cells and decreased autophagy. Knockdown of HIF1A-AS2 has also affected the expression of several genes that will increase drug sensitivity and inhibit autophagy in both cell lines. The levels of HIF-1α and Beclin-1 were decreased in both cell lines by knockdown of HIF1A-AS2. MRP1 expression was decrease in H69AR cells. In addition, CoCl2-induced hypoxic environment decreased in doxorubicin sensitivity of H69 cells, and knockdown of HIF1A-AS2 reversed this effect of hypoxia. Knockdown of HIF1A-AS2 increased drug sensitivity of SCLC cells in relation to autophagy. Therefore, hypoxia-HIF1A-AS2-autophagy interaction is thought to be determinative in drug sensitivity of these cells.

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Acknowledgements

This study was produced from the PhD thesis of Ebru Güçlü and supported by Necmettin Erbakan University, Scientific Research Projects (#181418001).

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Authors and Affiliations

  1. Department of Medical Biology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Ebru Güçlü, Canan Eroğlu Güneş, Ercan Kurar & Hasibe Vural

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  1. Ebru Güçlü
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  2. Canan Eroğlu Güneş
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Contributions

EG: conceptualization, investigation, methodology, formal analysis, writing—original draft, writing—review & editing, visualization. CEG: investigation, formal analysis, visualization. EK: resources, writing—review & editing. HV: resources, writing—review & editing, supervision.

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Correspondence to Ebru Güçlü.

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Güçlü, E., Eroğlu Güneş, C., Kurar, E. et al. Knockdown of lncRNA HIF1A-AS2 increases drug sensitivity of SCLC cells in association with autophagy. Med Oncol 38, 113 (2021). https://doi.org/10.1007/s12032-021-01562-2

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