Knockdown of cir_RNA PVT1 Elevates Gastric Cancer Cisplatin Sensitivity via Sponging miR-152-3p

Abstract

Background: Cisplatin (DDP) resistance is a key problem for effective treatment of gastric cancer (GC). Circular RNA PVT1 (circPVT1) acts as a vital regulator in the progression and development of various cancers. However, the in-depth mechanism of circPVT1 in GC resistance to DDP is still unclear.

Materials and methods: Quantitative real-time polymerase chain reaction was executed for the detection of the expression of circPVT1, miR-152-3p, and hepatoma-derived growth factor (HDGF) mRNA in GC tissues and cells. Western blot was used to detect the levels of HDGF protein, Bax, cleaved-casp-3, Bcl-2, p-PI3K, and p-AKT in tissue samples and/or cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to determine the viability, proliferation, and apoptosis of DDP-resistant GC cells. The relationship between miR-152-3p and circPVT1 or HDGF was confirmed by dual-luciferase reporter assay. The biological role of circPVT1 in vivo was confirmed with a xenograft tumor model.

Results: CircPVT1 and HDGF mRNA were upregulated while miR-152-3p was downregulated in chemoresistance tissues and DDP-resistant GC cells. Both circPVT1 and HDGF inhibition elevated cell sensitivity to DDP, suppressed cell viability, proliferation, and induced cell apoptosis in DDP-resistant GC cells. The MiR-152-3p inhibitor reversed the influence of circPVT1 silencing on DDP sensitivity, viability, proliferation, and apoptosis of DDP-resistant GC cells. Moreover, circPVT1 regulated the HDGF/PI3K/AKT pathway through sponging miR-152-3p. In addition, circPVT1 knockdown reduced the malignancy of DDP-resistant GC cells in vivo.

Conclusions: CircPVT1 regulated the chemoresistance and malignancy of GC through modulating HDGF expression via sponging miR-152-3p, providing a theoretical basis for the development of effective therapeutic strategies for GC.

Keywords: DDP; GC; HDGF; circPVT1; miR-152-3p.