Circular RNA-AnnexinA7 accelerates cisplatin resistance in non-small cell lung cancer via modulating microRNA-545-3p...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
• Cisplatin (DDP) is a cornerstone chemotherapy agent, but acquired DDP resistance significantly limits its clinical efficacy.
• Understanding the molecular mechanisms underlying DDP resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To elucidate the role of circular RNA AnnexinA7 (circ-ANXA7) in mediating DDP resistance in NSCLC.
• To investigate the interaction between circ-ANXA7, microRNA-545-3p (miR-545-3p), and Cyclin D1 (CCND1) in the context of DDP resistance.
• To explore the potential of circ-ANXA7 as a therapeutic target for overcoming DDP resistance in NSCLC.

Main Methods:

• Comparative analysis of circ-ANXA7, miR-545-3p, and CCND1 expression in NSCLC tissues and cell lines with varying DDP sensitivity.
• In vitro assays including MTT, colony formation, flow cytometry, Transwell migration, and invasion assays to assess cell proliferation, apoptosis, migration, and invasion.
• Verification of the targeting relationships between circ-ANXA7, miR-545-3p, and CCND1 using molecular biology techniques.
• In vivo studies involving tumor xenografts in mice to evaluate the effect of circ-ANXA7 on tumor growth.

Main Results:

• Circ-ANXA7 and CCND1 expression were significantly upregulated, while miR-545-3p was downregulated in DDP-resistant NSCLC tissues and cells.
• Circ-ANXA7 directly interacted with miR-545-3p, leading to the suppression of miR-545-3p's inhibitory effect on CCND1.
• Overexpression of circ-ANXA7 promoted NSCLC cell proliferation, migration, invasion, and DDP resistance, while inhibiting apoptosis.
• In vivo experiments confirmed that circ-ANXA7 contributes to tumor growth in DDP-resistant NSCLC.

Conclusions:

• Circ-ANXA7 plays a critical role in promoting DDP resistance in NSCLC by acting as a molecular sponge for miR-545-3p, thereby upregulating CCND1.
• The circ-ANXA7/miR-545-3p/CCND1 axis represents a novel mechanism contributing to chemoresistance in NSCLC.
• Circ-ANXA7 emerges as a promising therapeutic target for overcoming DDP resistance and improving treatment outcomes in NSCLC patients.