Guanosine monophosphate synthase upregulation mediates cervical cancer progression by inhibiting the apoptosis of cervical cancer cells via the Stat3/P53 pathway

Abstract

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.

H2S-Synthesizing Enzymes Are Putative Determinants in Lung Cancer Management toward Personalized Medicine

“…Guanosine is a purine needed for different cellular processes, namely, the synthesis of nucleotides. In cancer, the upregulation of guanosine monophosphate synthase has been described and related to apoptosis inhibition and chemoresistance [68,69]. In SCLC, chemoresistant tumors present high levels of guanosine nucleotides [70].…”

Whole-Genome Sequencing of 100 Genomes Identifies a Distinctive Genetic Susceptibility Profile of Qatari Patients with Hypertension

“…The association between these loci and hypertension risk has not been reported in the medical literature. GMPS (guanine monophosphate synthesis) is engaged in guanine nucleotide de novo synthesis providing GTP, which is involved in cellular processes that are critical for cell division [ 44 ]. GTP is the primary source of cyclic guanosine monophosphate (cGMP), which catalyzes a variety of cardio-protective functions [ 45 ].…”

GMP Synthetase: Allostery, Structure, and Function

“…An impairment in the growth of C. difficile and its reduced capacity to colonize the mouse gut upon the inactivation of GMP synthetase demonstrates the importance of de novo GMP biosynthesis and the possibility of targeting guanine riboswitches with suitable analogues [ 11 ]. In rapidly proliferating cells, there is increased activity of the enzymes involved in nucleotide metabolism due to the need for increased levels of nucleotides, making these enzymes, including GMPS, potential drug targets for both anti-cancer and immunosuppressive chemotherapies [ 12 , 13 , 14 , 15 ].…”