Downregulation of GMPS inhibited the proliferation of hepatocellular cancer cells via the regulation of STAT3/c-Myc pathway
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Hepatocellular cancer (HCC) is the sixth most common type of cancer worldwide. Guanosine monophosphate synthase (GMPS) participates in the regulation of chromatin and genes in various organisms, and is highly expressed in a number of human malignant tumors. However, the role of GMPS in HCC has not yet been fully studied and clarified. In this study, the differential fold changes in gene expression levels between HCC cancer tissues and correspondent adjacent normal tissue in The Cancer Genome Atlas Program and GEO datasets were analyzed using R language. GMPS expression levels in HCC cells were knocked down using specific siRNAs. In addition, CCK-8, EdU, TUNEL and immunofluorescence staining were conducted to explore the effects of GMPS siRNAs on HCC cell viability, proliferation, apoptosis and the STAT pathway level, respectively. The results indicated GMPS expression was significantly increased in HCC tumor tissues compared with the corresponding adjacent normal tissues. In addition, high expression of GMPS is negatively associated with the survival rate of patients with HCC. In vitro studies illustrated the knockdown of GMPS notably prevented HCC cell proliferation and induced HCC cell (Hep3B2.1-7 and MHCC97H) apoptosis by regulating the STAT3/c-Myc pathway. The apoptosis-specific marker cleaved caspase was significantly upregulated by GMPS knockdown in HCC cells. The findings of the present study revealed the association between GMPS and the prognosis of HCC. The results suggested that GMPS may serve as a promising marker for the prognosis of HCC, and it may also be a potential therapeutic target for HCC. These findings may lay the theoretical foundation for the clinical application of GMPS.
CRediT authorship contribution
Lin Liua, Wei Huang, methodology, writing – original draft. Yu Wu, Guanlong Yea, Jing Zhanga, Tong Shen, investigation, data collection and analysis. Changjuan Ouyang, supervision, validation, writing – original draft. All authors have read and approved the final version of the manuscript.
Data Availability Statement
The data generated in the present study may be requested from the corresponding author.
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