CircGOT1 promotes cell proliferation, mobility, and glycolysis-mediated cisplatin resistance via inhibiting its host gene GOT1 in esophageal squamous cell cancer.

Shasha Zhou, Zhiyuan Guo, Xueli Lv, Xueqiang Zhang

Cell cycle (Georgetown, Tex.) 2022 Feb

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Esophageal squamous cell cancer (ESCC) is a prevalent malignant cancer with high incidence and fatality rate. Surging evidences have revealed that circular RNAs (circRNAs) act key role in ESCC tumorigenesis and progression. Therefore, the purpose of this study is to explore the role and regulatory mechanism of a novel circGOT1 in ESCC. In the present study, the transcriptional expression of circGOT1, miR-606 and GOT1, and the epithelial-mesenchymal transition (EMT) and apoptosis-related markers were examined by quantitative PCR. The protein levels of GOT1 and glycolysis-related proteins were detected by Western blotting. In addition, the glycolytic levels were determined via measuring glucose uptake, lactate production, and ATP levels. Then, the function experiments and rescue experiments were used to investigate the function and mechanism of circGOT1 in ESCC. In addition, RNA immunoprecipitation, pull-down, and luciferase activity reporter gene assays were used to analyze the circGOT1/miR-606/GOT1 axis. The xenograft mouse mode was used to determine the function of circGOT1 in vivo. Here, we identified that circGOT1 and GOT1 upregulate, whereas miR-606 was reduced in ESCC tissues and cell lines. High circGOT1 and GOT1 expression associated with poor survival and worse prognosis of ESCC patients, but miR-606 revealed opposite traits. Mechanically, circGOT1 sponged miR-606 to promote GOT1, which induced cell proliferation, migration, aerobic glycolysis, and cisplatin resistance. The tumor growth was reduced by circGOT1 inhibition in xenograft mouse. Our results indicate the oncogene role of circGOT1 in ESCC via an endogenous competition RNA (ceRNA) mechanism to promote GOT1 expression via sponging miR-606.

Citation

Shasha Zhou, Zhiyuan Guo, Xueli Lv, Xueqiang Zhang. CircGOT1 promotes cell proliferation, mobility, and glycolysis-mediated cisplatin resistance via inhibiting its host gene GOT1 in esophageal squamous cell cancer. Cell cycle (Georgetown, Tex.). 2022 Feb;21(3):247-260