GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation.

TPX2 expression is associated with proliferation, apoptosis, and EMT in hepatocellular carcinoma cell and patients.

GA can inhibit CCl4-induced hepatocyte apoptosis via a p53-dependent mitochondrial pathway to retard the progress of liver fibrosis in rats.

Kinesin family member C1 (KIFC1, also known as HSET) is a minus end-directed motor protein, which is critical in centrosome clustering. The present study investigated the expression of KIFC1 in paired hepatocellular carcinoma (HCC) tissues and adjacent non-cancerous tissues from 91 patients by immunohistochemical analysis; clinical data were concomitantly collected. KIFC1 was expressed at high levels in HCC tissues, compared with that in peritumoral tissues (54.9 vs. 14.3%; P<0.01), and its expression correlated with tumor emboli, metastasis, recurrence and time of recurrence. Kaplan-Meier analysis showed that the expression of KIFC1 was significantly associated with tumor-free survival rates. In addition, multivariate analyses revealed that the overexpression of KIFC1was an independent predictive marker in patients with HCC. Consistently, data derived from GEPIA was in agreement with the results. In vitro, KIFC1 knockdown effectively decreased HCC cell viability, and induced apoptosis and cell death. KIFC1 knockdown also significantly suppressed tumor cell migration and invasion in vitro. Mechanistically, the apoptosis-related protein, B-cell lymphoma-2 (Bcl-2), was downregulated in KIFC1 small interfering RNA-treated groups, whereas thee levels of Bcl-2-associated X protein and p53 were upregulated. In addition, the expression levels of phosphorylated phosphoinositide 3-kinase and phosphorylated AKT were decreased significantly when KIFC1 was silenced. The epithelial-mesenchymal transition-related proteins, N-cadherin, matrix metalloproteinase-2 (MMP-2), β-catenin, Slug, and Zinc finger E-box-binding homeobox 1, were downregulated, whereas the expression of E-cadherin was upregulated. The overexpression of KIFC1 was correlated closely with the progression of HCC and poor prognosis, and suggested that the expression levels of KIFC1 are a potential prognostic biomarker and therapeutic target in HCC.

BackgroundThe application of microRNAs (miRNAs) as potential biomarkers and therapy targets has been widely investigated in many kinds of cancers. The discovery of tumor associated miRNAs in serum of patients supported the use of plasma/serum miRNAs as noninvasive means of cancer detection. However, the aberrant expression of miRNAs in bladder cancer patients and their intensive roles and mechanisms in bladder cancer are poorly understood.MethodsTaqman probe stem-loop real-time PCR was used to accurately measure the levels of miR-19a in bladder cancer cell lines, 100 pairs of bladder cancer tissues and the adjacent non-neoplastic tissues and also the plasma collected from bladder cancer patients and normal controls. miR-19a mimics and inhibitors were transfected into bladder cancer cells to investigate its role on regulating cell proliferation which was measured by CCK-8 and colony formation assay. The target of miR-19a was identified by western blot and whether its regulatory role depends on its target was improved by a rescue experiment with miR-19a mimic and PTEN expression plasmid.ResultsmiR-19a was significantly up-regulated in bladder cancer tissues and high-level of miR-19a was correlative with more aggressive phenotypes of bladder cancer. Meanwhile, gain or loss of function of miR-19a demonstrated that miR-19a can promote cell growth of bladder cancer cells and the further mechanism studies indicated that its oncogenic role was dependent on targeting PTEN. Furthermore, investigation of miR-19a expression in the plasma of bladder cancer patients showed that miR-19a was also increased in plasma of bladder cancer patients which strongly supported miR-19a could be developed as potential diagnostic marker of bladder cancer.ConclusionsOur data indicated that miR-19a might act as an oncogenic microRNA in bladder cancer and was significantly up-regulated in bladder cancer carcinogenesis. The oncogenic role of miR19a in bladder cancer was dependent on targeting PTEN.

The survival and colonization of tumor cells at new locations involve a variety of complex genetic, epigenetic, and microenvironmental factors. TRIM24 was originally named transcription intermediary factor 1-alpha (TIF1α), which was associated with cellular proliferation and was an oncogene in tumor development. Here we provide the first evidence of the expression profile and clinicopathological significance of TRIM24 in patients with hepatocellular carcinoma (HCC). Immunohistochemistry was employed to determine the expression level of TRIM24 in HCC tissues and noncancerous liver tissues. Elevated TRIM24 level was found in 61.4% HCC samples (51/83) correlating with AFP (P = 0.036), poor differentiation (P = 0.004), intrahepatic metastasis (P = 0.004), recurrence (P = 0.000006), and shorter tumor-free survival time (P = 0.002). Small interfering RNA induced down-regulation of TRIM24 promoted apoptosis in HCC cell line HepG2. Moreover, western blotting analysis revealed that knockdown of TRIM24 increased the protein levels of p53, Bax, and Caspase-8, and decreased Bcl-2, Survivin, Cyclin D1, and CDK4. Depletion of TRIM24 decreased Snail, Slug, β-catenin, and Vimentin, and increased E-cadherin expression, which suggested the involvement of TRIM24 in EMT. These results indicated that TRIM24 plays an important role in the pathogenesis of human HCC.

The non-SMC condensin I complex subunit G (NCAPG) that organizes the coiling topology of individual chromatids, represents an overexpressed antigen in various types of cancer, and also contributes to restructuring chromatin into rod-shaped mitotic chromosomes and ensuring the segregation of sister chromatid during cell division. In this study, we investigated the association between NCAPG expression and the biological behavior of hepatocellular carcinoma (HCC) to further explore the potential of NCAPG as a therapeutic target. The expression of NCAPG was detected in human HCC cell lines and tumor samples. The effects of NCAPG on the cell cycle, apoptosis and metastasis were investigated by various assays. NCAPG was found to be overexpressed in HCC compared with the adjacent normal tissue (P<0.001), and high levels of NCAPG expression were found to significantly correlate with recurrence, the time of recurrence, metastasis, differentiation and TNM stage. Furthermore, an elevated expression of NCAPG was associated with a poor overall survival (P<0.05). In addition, in vitro experiments further confirmed the ex vivo data; i.e., the knockdown of NCAPG expression reduced HCC cell viability, but induced apoptosis and arrested the cells at the S phase of the cell cycle. The knockdown of NCAPG expression also inhibited tumor cell migration and the cell invasive capacity in vitro. At the protein level, the knockdown of NCAPG expression upregulated Bax, cleaved caspase-3 and E-cadherin, but downregulated cyclin A1, CDK2, Bcl-2, N-cadherin and HOXB9 expression, suggesting that the knockdown of NCAPG expression suppressed tumor cell epithelial-mesenchymal transition. On the whole, this study demonstrates that NCAPG plays an important role in the development and progression of HCC, and that it may be a novel therapeutic target for patients with HCC.

Secretory clusterin (sClu) is an anti-apoptotic protein that plays a role in protecting cells from Tumour-necrosis factor (TNF)-alpha-induced apoptosis. The aim of the present study was to investigate the molecular mechanisms underlying the effect of sClu on TNF-alpha-induced apoptosis in breast cancer cells. The wild-type p53 expressing MCF-7 cell line was engineered to overexpress sClu (MCF-7/sClu), whereas the MDA-MB-231 cell line with mutant p53 was transfected with a sClu silencing siRNA (MDA-MB-231/sClu siRNA). The effects of clusterin overexpression and downregulation on apoptosis and sensitivity to TNF-alpha were examined in vitro. Our results showed that TNF-alpha treatment increased Bcl-2 mRNA and protein levels in breast cancer cells, suggesting that Bcl-2 is directly regulated by nuclear factor-kappaB (NF-kappaB) in response to TNF-alpha. The induction of Bcl-2 was mediated by the p65 subunit of NF-kappaB. siRNA-mediated silencing of Bcl-2 led to a significant increase in TNF-alpha-induced apoptosis. Silencing of sClu in MDA-MB-231/sClu siRNA cells abrogated TNF-alpha-mediated NF-kappaB activation and Bcl-2 overexpression, and rendered the MDA-MB-231/sClu siRNA cells significantly more sensitive to TNF-alpha-mediated apoptosis than the parental cells. Furthermore, overexpression of sClu in MCF-7/sClu cells promoted TNF-alpha-mediated NF-kappaB activity and Bcl-2 overexpression, and rendered the MCF-7/Clu cells significantly more resistant to TNF-alpha-mediated apoptosis. Inhibition of NF-kappaB activity or p65 and Bcl-2 expression reversed these effects. The present results suggested that sClu confers breast cancer cells resistance to TNF-alpha-induced apoptosis through NF-kappaB activation and Bcl-2 overexpression.