Gas7 attenuates hepatocellular carcinoma progression and chemoresistance through the PI3K/Akt signaling pathway

• Published in: Cellular signalling Vol. 112; p. 110908
• Main Authors: Liu, Wen-Feng, Zhang, Qi-Wei, Quan, Bing, Zhang, Feng, Li, Miao, Lu, Shen-Xin, Dong, Ling, Yin, Xin, Liu, Bin-Bin
• Format: Journal Article
• Language: English
• Published: England 01.12.2023
• Subjects: Carcinoma, Hepatocellular - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Movement; Cell Proliferation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms - genetics; Oxaliplatin - pharmacology; Oxaliplatin - therapeutic use; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; PI3K/Akt signaling pathway; Hepatocellular carcinoma; Gas7
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2023.110908

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.