Department of Oncology, Dongying People's Hospital, Dongying, Shandong Province, China.
Department of Blood Transfusion, Dongying People's Hospital, Dongying, Shandong Province, China.
J Surg Res. 2021 May;261:185-195. doi: 10.1016/j.jss.2020.12.013. Epub 2021 Jan 12.
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.
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.
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.
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.
顺铂（DDP）耐药性是有效治疗胃癌（GC）的关键问题。环状 RNA PVT1（circPVT1）在各种癌症的进展和发展中起着重要的调节作用。然而，circPVT1 在 GC 对 DDP 耐药中的深入机制仍不清楚。
通过定量实时聚合酶链反应检测 GC 组织和细胞中 circPVT1、miR-152-3p 和肝癌衍生生长因子（HDGF）mRNA 的表达。Western blot 用于检测组织样本和/或细胞中 HDGF 蛋白、Bax、cleaved-casp-3、Bcl-2、p-PI3K 和 p-AKT 的水平。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和流式细胞术检测 DDP 耐药 GC 细胞的活力、增殖和凋亡。通过双荧光素酶报告基因实验证实了 miR-152-3p 与 circPVT1 或 HDGF 的关系。通过异种移植肿瘤模型证实了 circPVT1 在体内的生物学作用。
耐药组织和 DDP 耐药 GC 细胞中 circPVT1 和 HDGF mRNA 上调，而 miR-152-3p 下调。circPVT1 和 HDGF 抑制均提高了 DDP 耐药 GC 细胞对 DDP 的敏感性，抑制了细胞活力、增殖，并诱导 DDP 耐药 GC 细胞凋亡。miR-152-3p 抑制剂逆转了 circPVT1 沉默对 DDP 耐药 GC 细胞 DDP 敏感性、活力、增殖和凋亡的影响。此外，circPVT1 通过海绵 miR-152-3p 调节 HDGF/PI3K/AKT 通路。此外，circPVT1 敲低降低了 DDP 耐药 GC 细胞在体内的恶性程度。
circPVT1 通过调节 HDGF 的表达来调节 GC 的化疗耐药性和恶性程度，通过海绵 miR-152-3p，为 GC 有效治疗策略的发展提供了理论依据。
