• Xun Wang, Fang-Yuan Li, Wei Zhao, Zhi-Kang Gao, Bin Shen, Hao Xu, and Yan-Feng Cui.
• Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
• Int J Exp Pathol. 2020 Dec 1; 101 (6): 215-222.

AbstractTumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC, si-GAS5, si-PTEN or si-Ctrl. A human liver cancer cell line (SMCC-7721) was incubated with the modified TAM supernatant. Quantitative real-time PCR and Western blot were performed to detect gene and protein expression. The cell proliferation and invasion properties of the SMCC-7721 cells were detected by MTT and Transwell assays. GAS5 is up-regulated in M1 macrophages and down-regulated in M2 macrophages and TAMs. GAS5 overexpression promoted M1-like polarization of TAMs and inhibited M2-like polarization of TAMs. Moreover, GAS5 promoted the expression of PTEN in TAMs. PTEN-silenced TAM supernatant treatment promoted cell proliferative and invasive properties of the SMCC-7721 cells and diminished the effect of GAS5-overexpressed TAM supernatant on the cell proliferation and invasion by SMCC-7721 cells. Our results demostrared that GAS5 overexpression inhibited M2-like polarization of TAMs by enhancing PTEN expression, thereby inhibiting cell proliferation and invasion by SMCC-7721 cells. Thus, our results suggest that GAS5 may be a new therapeutic target for HCC treatment.© 2020 Company of the International Journal of Experimental Pathology (CIJEP).

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