Knockdown of Long Non-Coding RNA Suppresses Cisplatin Resistance, Cell Proliferation, Migration and Invasion of DDP-Resistant NSCLC Cells by Targeting Axis.

BACKGROUND

Long non-coding RNA (lncRNA) 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 , and () 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 and either or was predicted on Diana Tools website, and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation.

RESULTS

Expression of was upregulated in DDP-resistant NSCLC tumor tissues and cell lines (A549/DDP and H1299/DDP). Knockdown of 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, negatively regulated expression via targeting, and DCLK1 was a downstream target for miR-149-5p. was indirectly regulated by in DDP-resistant NSCLC cells as well. Functionally, deletion could counteract the inhibitory effect of HOTAIR knockdown on cisplatin resistance; contrarily, restoring exhibited the similar inhibition on cisplatin resistance in DDP-resistant cells in vitro, which was then abated by upregulation.

CONCLUSION

Knockdown of enhances DDP-resistant NSCLC cells to overcome cisplatin resistance partially via regulating / axis.