circPDK1 competitively binds miR-4731-5p to mediate GIGYF1 expression and increase paclitaxel sensitivity in...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Paclitaxel (PTX) resistance is a major challenge in treating non-small cell lung cancer (NSCLC).
• Circular RNAs (circRNAs) play critical roles in cancer progression and drug resistance.
• The specific role of circPDK1 in PTX resistance in NSCLC remains largely unexplored.

Purpose of the Study:

• To elucidate the function of circPDK1 in the development of paclitaxel resistance in non-small cell lung cancer.
• To investigate the molecular mechanism underlying circPDK1-mediated PTX resistance.

Main Methods:

• Quantitative real-time PCR and Western blot were used to measure circPDK1, miR-4731-5p, and GIGYF1 expression.
• Cell proliferation, apoptosis, and invasion assays were performed to assess cellular responses.
• Dual luciferase reporter and RIP assays confirmed the targeting interactions between molecules.
• A xenograft tumor model was utilized to evaluate the in vivo effect of circPDK1 suppression.

Main Results:

• circPDK1 was found to be upregulated in PTX-resistant NSCLC cells.
• Knockdown of circPDK1 inhibited proliferation and invasion, induced apoptosis, and increased PTX sensitivity in resistant cells.
• circPDK1 directly targets miR-4731-5p, which in turn targets GIGYF1.
• Upregulating GIGYF1 reversed the effects of circPDK1 knockdown on PTX sensitivity.
• In vivo studies confirmed that suppressing circPDK1 inhibits tumor growth and enhances PTX efficacy.

Conclusions:

• circPDK1 promotes paclitaxel resistance in NSCLC by sponging miR-4731-5p and upregulating GIGYF1.
• Targeting the circPDK1/miR-4731-5p/GIGYF1 axis represents a promising therapeutic strategy to overcome PTX resistance in NSCLC.