BackgroundReduced 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.MethodsThe protein levels of TRIM3 in five liver cancer cell lines (SK-Hep1, Hep3B, 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 Hep3B 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 of TRIM3 on tumor growth and metastases in nude mice was also investigated.ResultsTRIM3 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 G0/G1 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 Hep3B cells by siTRIM3 led to significantly decreased percentages of both cells in the G0/G1 phase and promoted cell proliferation, colony formation, migration, and invasion. In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis.ConclusionsTRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G0/G1 phase.

This study aimed at investigating the clinical significance and biological function of ubiquitination factor E4B (UBE4B) in human renal cell carcinoma (RCC). Methods: 19 paired clear cell renal cell carcinoma (ccRCC) tumor samples and the matched neighboring non-tumor samples were used to detect the expression of UBE4B in RCC tumor by Western blotting and RT-qPCR. UBE4B expression was also detected in 151 ccRCC paraffin-embedded tumor samples by using immunohistochemistry. Overall survival (OS) in different UBE4B expression groups were compared with Log rank test. The prognostic value of UBE4B expression in OS was evaluated with the univariate and multivariate Cox regression models. UBE4B was knocked down by small interfering RNA (siRNA) technology, and the effect of UBE4B on cell proliferation, colony formation, metastasis, apoptosis and cell cycle of RCC cells were examined in vitro. Results: Both protein and mRNA levels of UBE4B were up-regulated in ccRCC tumor tissues in contrast to the corresponding adjacent nontumor ones. UBE4B expression was positively associated with tumor-node-metastasis (TNM) stage and distant metastasis in ccRCC patients. Survival analyses indicated that low expression of UBE4B was associated with increased OS in ccRCC patients. Functional analyses demonstrated that siRNA silencing of UBE4B expression in SKRC39 and ACHN cells further reduced the growth, motility and invasiveness of RCC cells. Moreover, siRNA silencing of UBE4B in the RCC cell lines did not induce apoptosis, and an increase in the cell population was observed during the G 0 /G 1 phase of the cell cycle. Conclusion: UBE4B might act as an oncogene in regulating RCC development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of RCC patients.

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Despite advancements made in the therapeutic strategies on hepatocellular carcinoma (HCC), the survival rate of HCC patient is not satisfactory enough. Therefore, there is an urgent need for the valuable prognostic biomarkers in HCC therapy. In this study, we aimed to screen hub genes correlated with prognosis of HCC via multiple databases. 117 HCC-related genes were obtained from the intersection of the four databases. We subsequently identify 10 hub genes (JUN, IL10, CD34, MTOR, PTGS2, PTPRC, SELE, CSF1, APOB, MUC1) from PPI network by Cytoscape software analysis. Significant differential expression of hub genes between HCC tissues and adjacent tissues were observed in UALCAN, HCCDB and HPA databases. These hub genes were significantly associated with immune cell infiltrations and immune checkpoints. The hub genes were correlated with clinical parameters and survival probability of HCC patients. 147 potential targeted therapeutic drugs for HCC were identified through the DGIdb database. These hub genes could be used as novel prognostic biomarkers for HCC therapy.