Published in:
Open Access 01-12-2022 | Hepatocellular Carcinoma | Primary Research
FOXM1-induced TYMS upregulation promotes the progression of hepatocellular carcinoma
Published in: Cancer Cell International | Issue 1/2022
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Background
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the major causes of cancer-related death. Thymidylate synthase (TYMS) catalyzes the methylation of deoxy guanosine to deoxy thymidylate, which is a crucial gene for DNA repair and replication. Thus, TYMS was reported to be closely associated with developing a variety of tumors, but it has been poorly studied in HCC.
Materials and methods
We used the cell counting kit-8 (CCK-8), BrdU, and CFSE assay to measure cell proliferation. The flow cytometry assay and the TUNEL assay were used for assessing cell apoptosis. The flow cytometry assay was used to analyze the cell cycle. The Transwell invasion assay and the wound healing assay were conducted to determine the invasive ability of the cells. RT-qPCR and Western blot analyses were performed to evaluate the mRNA and protein expression levels of specific genes, respectively.
Results
TYMS was found to be upregulated in both HCC cells and patient samples. High expression of TYMS was associated with an unfavorable prognosis in HCC patients based on the TCGA-LIHC dataset. Cell proliferation, apoptosis, and invasion assays revealed that TYMS promoted the proliferation and invasion of HCC cells as well as inhibited apoptosis. In addition, TYMS is a downstream target of FOXM1. TYMS knockdown reversed the 5-FU resistance caused by FOXM1 overexpression and re-sensitized HCC cells to 5-FU treatment.
Conclusion
This study suggested that TYMS serves as an oncogene in HCC, and targeting the FOXM1-TYMS axis may help improve the survival of HCC patients as well as provide new insights for treating advanced HCC patients.