Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly red...Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma(HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients.However,the role of TRIM3 in liver cancer remains unknown.This study aimed to investigate the function of TRIM3 in liver cancer cells.Methods:The protein levels of TRIM3 in five liver cancer cell lines(SK-Hep1,Hep3 B,Huh7,HepG2,Bel-7402) and one normal liver cell line(L02) were detected with Western blotting.HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3(LV-TRIM3),whereas Huh7 and Hep3 B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA(siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were examined.The effect ofTRIM3 on tumor growth and metastases in nude mice was also investigated.Results:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell lines.Cell cycle analysis showed that TRIM3 overexpression induced G_0/G_1 phase arrest in HepG2 and Bel-7402 cells.Moreover,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3.Contrarily,silencing TRIM3 expression in Huh7 and Hep3 B cells by siTRIM3 led to significantly decreased percentages of both cells in the G_0/G_1 phase and promoted cell proliferation,colony formation,migration,and invasion.In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis.Conclusions:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G_0/G_1 phase.展开更多
基金primarily supported by grants from the National Natural Science Foundation of China(Nos.81472387 and 81402560)Guangdong Province Science and Technology Plan Project(No.2012A030400059)
文摘Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma(HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients.However,the role of TRIM3 in liver cancer remains unknown.This study aimed to investigate the function of TRIM3 in liver cancer cells.Methods:The protein levels of TRIM3 in five liver cancer cell lines(SK-Hep1,Hep3 B,Huh7,HepG2,Bel-7402) and one normal liver cell line(L02) were detected with Western blotting.HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3(LV-TRIM3),whereas Huh7 and Hep3 B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA(siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were examined.The effect ofTRIM3 on tumor growth and metastases in nude mice was also investigated.Results:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell lines.Cell cycle analysis showed that TRIM3 overexpression induced G_0/G_1 phase arrest in HepG2 and Bel-7402 cells.Moreover,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3.Contrarily,silencing TRIM3 expression in Huh7 and Hep3 B cells by siTRIM3 led to significantly decreased percentages of both cells in the G_0/G_1 phase and promoted cell proliferation,colony formation,migration,and invasion.In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis.Conclusions:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G_0/G_1 phase.
