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.
Keywords: HOTAIR , NSCLC, cisplatin resistance