Department of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Gynecology and Obstetrics, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224000, P.R. China.
Int J Oncol. 2021 Apr;58(4). doi: 10.3892/ijo.2021.5183. Epub 2021 Mar 2.
Guanosine monophosphate synthase (GMPS) participates in chromatin and gene regulation in multiple types of organisms, and is highly expressed in a variety of human malignancies. The purpose of the present study was to explore the expression of GMPS and its role in cervical cancer (CC), and to provide ideas for improving the clinical efficacy of CC treatment. In the present study, immunohistochemistry, reverse transcription‑quantitative PCR analysis, Cell Counting Kit‑8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, western blotting and immunofluorescence assays were conducted to detect the expression of GMPS in normal cervical tissues, CC tissues, para‑cancerous tissues and CC cell lines. Moreover, the present study detected the effect of GMPS knockdown on CC cell proliferation, clonal formation ability, aging and apoptosis, as well as on the expression levels of apoptosis‑related proteins in tumor cells. The present results demonstrated that the expression level of GMPS in CC was significantly higher compared with that of adjacent tissues; the expression rate of GMPS in CC was 57.36%. GMPS expression was found to successively and gradually increase from that in normal cervical tissues, to that in cervical intraepithelial neoplasia and CC tissues. The abnormal expression of GMPS was positively associated with the degree of CC differentiation and the depth of early invasion. Small interfering (si)RNA knockdown of GMPS inhibited proliferation and colony formation, and promoted aging and apoptosis of CC cells. Furthermore, subcutaneous injection of GMPS‑knockdown tumor cells in nude mice resulted in a decrease in the proliferative ability of the tumor. The animal experimental results showed that the tumor growth rate of the short hairpin (sh)RNA‑GMPS group was significantly slower than that of the HeLa sh‑negative control group. It was identified that GMPS may inhibit CC cell senescence and apoptosis via the Stat3/P53 molecular pathway. Collectively, the present results suggested that GMPS may be a marker of unfavorable prognosis of CC, and it may also be a potential therapeutic target for CC.
鸟苷酸单磷酸合酶（GMPS）参与多种生物的染色质和基因调控，在多种人类恶性肿瘤中高度表达。本研究旨在探讨 GMPS 在宫颈癌（CC）中的表达及其作用，为提高 CC 治疗的临床疗效提供思路。本研究采用免疫组织化学、反转录-定量 PCR 分析、细胞计数试剂盒-8 检测、5-乙炔基-2'-脱氧尿苷检测、流式细胞术、Western blot 及免疫荧光法检测 GMPS 在正常宫颈组织、CC 组织、癌旁组织及 CC 细胞系中的表达。此外，本研究还检测了 GMPS 敲低对 CC 细胞增殖、克隆形成能力、衰老和凋亡以及肿瘤细胞中凋亡相关蛋白表达水平的影响。结果表明，CC 中 GMPS 的表达水平明显高于相邻组织；CC 中 GMPS 的表达率为 57.36%。GMPS 的表达从正常宫颈组织、宫颈上皮内瘤变到 CC 组织呈逐渐升高趋势。GMPS 的异常表达与 CC 分化程度和早期浸润深度呈正相关。GMPS 的小干扰 RNA（siRNA）敲低抑制 CC 细胞的增殖和集落形成，并促进 CC 细胞衰老和凋亡。此外，裸鼠皮下注射 GMPS 敲低的肿瘤细胞导致肿瘤的增殖能力下降。动物实验结果表明，shRNA-GMPS 组的肿瘤生长速度明显慢于 HeLa sh-阴性对照组。研究结果表明，GMPS 可能通过 Stat3/P53 分子通路抑制 CC 细胞衰老和凋亡。综上所述，GMPS 可能是 CC 预后不良的标志物，也可能是 CC 的潜在治疗靶点。
