GAS5 Inhibitied M2 Type Polarization Of Tumor-related Macrophage In The Progression Of Hepatocellular Carcinoma

Objective: To investigate the effect of GAS5 on the M2 polarization of the tumor related macrophage(TAMs)in the progression of hepatocellular carcinoma(HCC).Methods: A total of 28 paired tissue samples from patients with hepatocellular carcinoma who were treated with hepatectomy in our hospital were collected.The infiltration of TAMs in tumor tissue were detected by immunohistochemistry.The peripheral blood mononuclear cells(PBMCs)were isolated and then induced to different phenotypes macrophages(M0,M1,M2 and TAMs).ELISA was used to detect the expression of secretory markers of macrophages.Four groups of macrophages with different phenotypes were co-cultured with HCCs.The proliferation,migration and invasion of HCCs were detected by MTT,scratch test and Transwell test,respectively.Next,we constructed the GAS5 expression plasmid and si RNA and transfected them into TAMs.The transfected TAMs were co-cultured with HCCs,which was aimed to analyze the effect of GAS5 on TAMs polarization and HCCs proliferation.Finally,we constructed GAS5 overexpression lentivirus and transfected TAMs.The xenograft tumor model was established by TAMs and HCCs suspension.Results: Comparing to the adjacent cancerous tissue,the TAMs was hathered in the tumor tissue.The different phenotypes macrophages were co-cultured with HCCs,and the results showed that the M2 type macrophages and TAMs both promoted the proliferation of HCCs.In addition,overexpression of GAS5 inhibits the differentiation of TAMs into M2 type,which have the same effect to M2 type macrophages and TAMs on HCCs.Further,in vivo xenograft tumor model showed that overexpression of GAS5 in TAMs could inhibit the growth of transplanted tumor in mice.Conclusion: The GAS5 expression was decreased in TAMs is associated with poor prognosis in HCC patients.Overexpression of GAS5 in TAMs can inhibit TAMs polarization into M2 and further inhibit the growth of HCC.