APOBEC3G exerts tumor suppressive effects in human hepatocellular carcinoma

Abstract

In this study, we collected 44 hepatitis B virus surface antigen positivity HBsAg (+) tumor and nontumor hepatocellular tissues from hepatocellular carcinoma (HCC) patients during hepatectomy, and quantified the APOBEC3G (A3G) mRNA by using a real-time PCR. Our results showed higher expression of A3G mRNA in the nontumor tissues than in the tumor tissues of the HBsAg (+) HCC patients. To further investigate this phenomenon, we constructed a pLV-A3G vector and transfected it into the human HCC cell line, Hep 3B. The results of an immunofluorescence analysis showed the overexpression of A3G in the cytoplasm. We then evaluated A3G cytotoxicity by using a cell viability assay (MTS assay), the results of which showed that Hep 3B cell viability was 88 and 58% after the transfection of pLV and pLV-A3G, respectively, indicating the growth inhibitory effects of A3G on Hep 3B cells. To further evaluate the tumor suppressive effects of A3G, we used a plastic pipette tip to scratch Hep 3B cells grown on a culture dish (to 70-80% confluence) after transfection with pLV-A3G. Our data indicated a ratio of wound closure of 100% in the control cells and in the pLV-expressing cells, compared with 43% in the pLV-A3G-overexpressing cells, 72 h after the wound scratch, as observed using phase-contrast microscopy. These results indicated that A3G inhibits wound healing in Hep 3B cells. Overall, our results suggest that A3G inhibits the growth of human hepatoma cells.

Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer

“…Due to the gene redundancy across immune gene sets, we identified “core genes” (genes associated with the enrichment signal) over-represented in different subsets for immune biological processes. The top-ten rank core genes included APOBEC3G (Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G) that exerts innate immune activity against retroviruses and has shown tumor suppressive effects in human hepatocellular carcinoma and enhance cell radio resistance in lymphomas; [ 8 , 9 ] APOBEC3F (Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3F) that showed to inhibit HIV-1 DNA Integration; [ 10 ] CCL5 (Chemokine (C-C motif) ligand 5, a well characterized chemotactic chemokine; CD1D (CD1d molecule) mediate the presentation of self or microbial antigens to T cells; LAT (Linker for activation of T cells), a major transporter for essential amino acids into activated human T cells; [ 11 ] TRAT1 (T cell receptor associated transmembrane adaptor 1), important to transport od CTLA-4 to the cell surface; [ 12 ] IL32 (Interleukin 32), whose expression is increased after the activation of T-cells by mitogens or the activation of NK cells by IL-2; CRTAM (cytotoxic and regulatory T cell molecule), upregulated in CD4 and CD8 T cells; CFHR1 (complement factor H-related 1), whose protein product binds to Pseudomonas aeruginosa elongation factor Tuf together with plasminogen and CCR2 (chemokine [C-C motif] receptor 2) that mediates monocyte infiltration. The complete list of core genes involved in immune gene sets is shown in Table S3 .…”

APOBEC3A Expression in Penile Squamous Cell Carcinoma

“…While similar suppressive effects on tumor cell growth have been reported for APOBEC3G [27], the widely accepted main oncogenic function of APOBEC3s is an induction of genome hypermutation [2]. There are therefore 2 scenarios to explain our findings.…”

Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer

“…29 , 30 However, another in vitro study found that high APOBEC3G expression reduced the migration ability of human hepatocellular carcinoma cells. 31 APOBEC3G gene and protein expression was significantly more abundant in melanoma compared to adjacent normal tissues, and its higher expression was associated with longer overall and recurrence‐free survival. Moreover, APOBEC3G expression is positively correlated with the infiltration of B cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells.…”

“…In colorectal cancer, APOBEC3G tissue protein expression was associated with poor prognosis and suggested to be mechanistically involved in the formation of liver metastasis 29,30 . However, another in vitro study found that high APOBEC3G expression reduced the migration ability of human hepatocellular carcinoma cells 31 . APOBEC3G gene and protein expression was significantly more abundant in melanoma compared to adjacent normal tissues, and its higher expression was associated with longer overall and recurrence‐free survival.…”