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

YunYin Feng; TaoLong Zhang; Hong Liu

doi:10.1007/s12672-024-01003-2

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

Discov Oncol. 2024 May 11;15(1):157. doi: 10.1007/s12672-024-01003-2.

Authors

YunYin Feng^#¹, TaoLong Zhang^#², Hong Liu^#³

Affiliations

¹ Department of Respiratory, Kaihua County Traditional Chinese Medicine Hospital, No.10 Zhongshan Road, Qinyang Office, Quzhou City, 324000, Zhejiang Province, China. Fyyin1406B@hotmail.com.
² Department of Gastroenterology, Kaihua County Traditional Chinese Medicine Hospital, Quzhou City, 324300, Zhejiang Province, China.
³ Department of Respiratory, Kaihua County Traditional Chinese Medicine Hospital, No.10 Zhongshan Road, Qinyang Office, Quzhou City, 324000, Zhejiang Province, China.

^# Contributed equally.

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.

Keywords: GIGYF1; Non-small cell lung cancer; Paclitaxel; circPDK1; miR-4731-5p.