Circular RNA PRMT5 knockdown enhances cisplatin sensitivity and immune response in non-small cell lung cancer by regulating miR-138-5p/MYH9 axis.

Abstract

Purpose: To explore the role and molecular mechanism of circRNA protein arginine methyltransferase-5 (circ-PRMT5) in regulating cisplatin (DDP) resistance and immune response of non-small cell lung cancer (NSCLC).

Methods: The expression of circ-PRMT5, miR-138-5p and myosin heavy chain 9 (MYH9) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, and western blot assay were utilized to evaluate DDP sensitivity. Interleukin 2 (IL-2), tumor necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β) production were measured by enzyme-linked immunosorbent assay (ELISA) to assess immune system's ability. A xenograft tumor model was established to explore the role of circ-PRMT5 in DDP resistance in vivo. The interaction between miR-138-5p and circ-PRMT5 or MYH9 was predicted by starBase and verified by dual-luciferase reporter assay.

Results: Circ-PRMT5 and MYH9 were upregulated and miR-138-5p was downregulated in DDP-resistant NSCLC tissues and cells. Circ-PRMT5 knockdown enhanced DDP sensitivity of NSCLC cells by inhibiting cell viability, migration and invasion and inducing apoptosis. Circ-PRMT5 knockdown also increased immune response by promoting the levels of IL-2 and TNF-a and decreasing the production of TGF-β. Moreover, circ-PRMT5 interference improved DDP sensitivity of NSCLC in vivo. MiR-138-5p was a direct target of circ-PRMT5 and its knockdown abated the effects of circ-PRMT5 downregulation on DDP resistance and immune response.

Conclusion: Circ-PRMT5 knockdown increased DDP sensitivity and immune response of NSCLC cells by regulating miR-138-5p/MYH9 axis, hinting potential value of circ-PRMT5 in the diagnosis and treatment for NSCLC.