circPDK1 competitively binds miR-4731-5p to mediate GIGYF1 expression and increase paclitaxel sensitivity in non-small cell lung cancer

Abstract

Abstract Objective To investigate the action of circPDK1 in paclitaxel (PTX) resistance in non-small cell lung cancer (NSCLC). Methods circPDK1, miR-4731-5p, and GIGYF1 levels were determined by RT-qPCR and Western blot. Cell proliferation was detected by CCK-8 and colony formation assay, apoptosis by flow cytometry, invasion by Transwell assay. The targeting relationship between miR-4731-5p and circPDK1 or GIGYF1 was confirmed by dual luciferase reporter gene and RIP assay. A xenograft tumor model was established to determine the role of circPDK1 in PTX resistance. Results circPDK1 was overexpressed in PTX-resistant NSCLC, and depleting circPDK1 hampered proliferation and invasion of PTX-resistant cells, activated apoptosis, and improved PTX sensitivity. circPDK1 bound to miR-4731-5p, and increasing miR-4731-5p expression salvaged the effect of circPDK1 depletion on PTX resistance. miR-4731-5p directly targeted GIGYF1, and upregulating GIGYF1 offset the promoting effect of circPDK1 knockdown on PTX sensitivity. NSCLC tumor growth was inhibited and PTX sensitivity improved when circPDK1 was suppressed. Conclusion Depleting circPDK1 promotes PTX sensitivity of NSCLC cells via miR-4731-5p/GIGYF1 axis, thereby inhibiting NSCLC pregnancy.