Knockdown of Long Non-Coding RNA HOTAIR Suppresses Cisplatin Resistance, Cell Proliferation, Migration and Invasion of DDP-Resistant NSCLC Cells by Targeting miR-149-5p/Doublecortin-Like Kinase 1 Axis
In: Cancer Management and Research, Jg. 12 (2020-08-01), S. 7725-7737
Online
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Zugriff:
Background Long non-coding RNA (lncRNA) HOTAIR has been reported to be associated with cisplatin (DDP) resistance in different human cancers including non-small cell lung cancer (NSCLC). However, the mechanism of HOTAIR in cisplatin resistance of NSCLC remains largely undefined. Materials and methods Expression of HOTAIR, miR-149-5p and doublecortin-like kinase 1 (DCLK1) was detected using real-time quantitative PCR (RT-qPCR) and Western blotting. Cisplatin resistance was determined with cell counting kit (CCK)-8 assay and transwell assays in vitro, and xenograft tumor models in vivo. The target binding between miR-149-5p and either HOTAIR or DCLK1 was predicted on Diana Tools website, and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. Results Expression of HOTAIR was upregulated in DDP-resistant NSCLC tumor tissues and cell lines (A549/DDP and H1299/DDP). Knockdown of HOTAIR decreased the acquired cisplatin resistance of A549/DDP and H1299/DDP cells, as evidenced by attenuated 50% inhibitory concentration (IC50) of DDP, cell proliferation, migration and invasion in vitro, as well as tumor growth inhibition in vivo. Mechanically, HOTAIR negatively regulated miR-149-5p expression via targeting, and DCLK1 was a downstream target for miR-149-5p. DCLK1 was indirectly regulated by HOTAIR in DDP-resistant NSCLC cells as well. Functionally, miR-149-5p deletion could counteract the inhibitory effect of HOTAIR knockdown on cisplatin resistance; contrarily, restoring miR-149-5p exhibited the similar inhibition on cisplatin resistance in DDP-resistant cells in vitro, which was then abated by DCLK1 upregulation. Conclusion Knockdown of HOTAIR enhances DDP-resistant NSCLC cells to overcome cisplatin resistance partially via regulating miR-149-5p/DCLK1 axis.
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Knockdown of Long Non-Coding RNA HOTAIR Suppresses Cisplatin Resistance, Cell Proliferation, Migration and Invasion of DDP-Resistant NSCLC Cells by Targeting miR-149-5p/Doublecortin-Like Kinase 1 Axis
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Autor/in / Beteiligte Person: | Shen, Yanli ; Zhan, Yiyi ; Liu, Chunling ; Wang, Xiuli ; Nuerlan, Saiteer ; Abuduwaili, Kahaerjiang |
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Zeitschrift: | Cancer Management and Research, Jg. 12 (2020-08-01), S. 7725-7737 |
Veröffentlichung: | Informa UK Limited, 2020 |
Medientyp: | unknown |
ISSN: | 1179-1322 (print) |
DOI: | 10.2147/cmar.s246299 |
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