The Expression and mechanism of Tim-3 in hepatocellular carcinoma

Abstract

Abstract: Objective To clarify the expression of TIM-3 in hepatocellular carcinoma (HCC) tissues, and investigate the malignant biological behavior of TIM-3-induced HCC cells in vitro and the possible mechanisms involved. Methods A total of 34 patients with primary HCC were enrolled who underwent surgical treatment for HCC from January 2021 to December 2021 in Nanjing Second Hospital. HCC tissues and adjacent neoplastic tissues were collected. The expression of TIM-3 in HCC tissues were detected by immunohistochemistry to analyze the correlation between TIM-3 expression and the clinicopathological parameters. Western blot was used to investigate the effect of TIM-3 expression and its binding to Galectin-9 on NF-κB/STAT3/IL-6 signaling axis. Results The expression of TIM-3 gene in tumor tissues was 73.5% (25/34), which was significantly higher than 50% (17/34) in normal tissues adjacent to cancer (χ²=3.985, P=0.046). The expression of TIM-3 in HCC tissues was significantly correlated with histological staging and clinical stage (χ²=7.404, 5.625, P<0.05). The increase rate and migration rateof HCC cells silenced with TIM-3 were significantly reduced (t=12.39, 3.129, P<0.05) . TIM-3 expression upregulated IL-6/STAT3/NF-κB-related proteins, and the expression of pathway-related proteins was inhibited after blocking Galectin-9. Conclusion TIM-3 is highly expressed in HCC tissues and promotes proliferation and migration of HCC cells. TIM-3 expression and interaction with Galectin-9 induce malignant biological progression of HCC cells by activating the IL-6/STAT3/NF-κB signaling axis.

Key words: TIM-3, Galectin-9, HCC, Biological behavior, Signaling pathway

ZHAO Tong, GUO Hai-ping, ZHENG Qin. The Expression and mechanism of Tim-3 in hepatocellular carcinoma[J]. Chinese Hepatolgy, 2024, 29(6): 671-675.

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