关键词: Gas7 Hepatocellular carcinoma PI3K/Akt signaling pathway

Mesh : Humans Carcinoma, Hepatocellular / genetics Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Movement Cell Proliferation Drug Resistance, Neoplasm Gene Expression Regulation, Neoplastic Liver Neoplasms / genetics Oxaliplatin / pharmacology therapeutic use Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Signal Transduction

来  源:   DOI:10.1016/j.cellsig.2023.110908

Abstract:
Growth arrest-specific gene 7 (Gas7) was involved in various cellular functions, although its specific roles and molecular mechanisms in hepatocellular carcinoma (HCC) remained unclear. So the current study was to investigate the role of Gas7 in HCC. Our findings revealed that Gas7 was downregulated in various HCC cell lines and low Gas7 expression was associated with decreased overall survival in patients with HCC. Additionally, our functional assays showed that Gas7 inhibited cell proliferation and migration, induced cell cycle arrest, apoptosis, and autophagy, and enhanced oxaliplatin sensitivity by inhibiting the PI3K/Akt signaling pathway. We also observed that transcription factorSp1 was responsible for inhibiting Gas7. These findings provide insights into the role and elucidated a potential mechanism of Gas7 in HCC progression and metastasis. It was also observed that the Sp1/Gas7/PI3K/Akt axis was critical for malignant phenotype and oxaliplatin sensitivity in HCC. Therefore, Gas7 can be considered as a prognostic predictor and therapeutic target for HCC.
摘要:
生长停滞特异性基因7(Gas7)参与各种细胞功能,尽管其在肝细胞癌(HCC)中的具体作用和分子机制尚不清楚。因此,目前的研究是探讨Gas7在肝癌中的作用。我们的发现表明,Gas7在各种HCC细胞系中下调,低Gas7表达与HCC患者总体生存率降低有关。此外,我们的功能分析显示Gas7抑制细胞增殖和迁移,诱导细胞周期停滞,凋亡,和自噬,并通过抑制PI3K/Akt信号通路增强奥沙利铂敏感性。我们还观察到转录因子Sp1负责抑制Gas7。这些发现为Gas7在HCC进展和转移中的作用提供了见解,并阐明了Gas7在HCC进展和转移中的潜在机制。还观察到Sp1/Gas7/PI3K/Akt轴对于HCC中的恶性表型和奥沙利铂敏感性是关键的。因此,Gas7可作为HCC的预后预测因子和治疗靶点。
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