Circular RNA-AnnexinA7 accelerates cisplatin resistance in non-small cell lung cancer via modulating microRNA-545-3p to mediate Cyclin D1

Abstract

Objective: To explore the mechanism of circular RNA (circRNA)-AnnexinA7 (ANXA7) in non-small cell lung cancer (NSCLC) cisplatin (DDP) resistance through microRNA (miR)-545-3p to target Cyclin D1 (CCND1). Methods: DDP-resistant and non-resistant NSCLC tissues and normal tissues were collected. DDP-resistant cells (A549/DDP and H460/DDP) were constructed. circ-ANXA7, miR-545-3p, CCND1, P-Glycoprotein, and glutathione S-transferase-π in tissues and cells were measured. Analysis of circ-ANXA7 ring structure was performed, as well as detection of circ-ANXA7 distribution in cells. Cell proliferation was detected by MTT and colony formation assay, apoptosis rate was detected by flow cytometry, and cell migration and invasion were evaluated by Transwell assay. The targeting relationship between circ-ANXA7, miR-545-3p and CCND1 was verified. Measurement of tumor volume and quality in mice was performed. Results: Circ-ANXA7 and CCND1 were elevated, while miR-545-3p was suppressed in DDP-resistant NSCLC tissues and cells. Circ-ANXA7 combined with miR-545-3p, which targeted CCND1 to expedite A549/DDP cell proliferation, migration, invasion, DDP resistance, but inhibited cell apoptosis. Conclusion: Circ-ANXA7 enhances DDP resistance in NSCLC via absorbing miR-545-3p to target CCND1 and might be a latent therapeutic target for NSCLC.

Role of circular RNAs in lung cancer

“…Low levels of circRABL2B in plasma exosomes could distinguish early stage lung-cancer patients, and it was revealed that circRABL2B counteracts lung cancer progression via MUC5AC (Mucin 5AC, Oligomeric Mucus/Gel-Forming)/integrin β4/pSrc/p53 axis, making the circRABL2B potential therapeutic target ( Lu et al, 2023 ). An acceleration to cisplatin resistance in NSCLC patients by circ-ANXA7 was also recently reported ( Yao et al, 2023 ). A mechanism behind this was concluded to be the regulation of CCND1 (Cyclin D1) by circ-ANXA7 via miR-545-3p sponging.…”