The development of molecular pathogenesis of hepatocellular carcinoma (HCC) is complex and involves alterations in the expression and conformation of assorted oncoproteins and tumor suppressors. Chaperonin containing TCP1 (CCT) is a cytolic molecular chaperone complex that is required for the correct folding of numerous proteins. In this study, we investigated a possible involvement of CCT subunit 8 (CCT8) in HCC development. Immunohistochemical analysis was performed in 102 human HCC samples. High CCT8 expression was detected in clinical HCC samples compared with adjacent noncancerous tissues. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. Western blot confirmed the high expression of CCT8 in HCC compared with adjacent normal tissue. Moreover, the biological significance of the aberrant expression of CCT8 was investigated in HCC cell lines. Expression of CCT8 was correlated directly with the histologic grades and tumor size of HCC and high expression of CCT8 was associated with a poor prognosis. CCT8 depletion by siRNA inhibited cell proliferation and blocked S-phase entry in HuH7 cells. These results suggested that CCT8 might be an oncogene and participate in HCC cell proliferation. These findings provide a potential therapeutic strategy for the treatment of HCC.
Glioma is one of the most common type of primary intracranial tumor. Although great advances have been achieved in treatment of glioma, the underlying molecular mechanisms remain largely unknown. Previous studies demonstrated that FBP1 is a transcriptional regulator of c-Myc and acts as an important prognostic indicator in many cancers. Our study aimed to assess the expression and function of FBP1 in human glioma. Immunohistochemical and Western blot analysis were performed in human glioma and normal brain tissues. High FBP1 expression (located in cell nuclei) was observed in 70 samples and its level was correlated with the grade of malignancy. A strongly positive correlation was observed between FBP1 and c-Myc (P = 0.005) and Ki-67 expression (P = 0.009). In a multivariate analysis, high FBP1 and c-Myc expressions were showed to be associated with poor prognosis in glioma. While in vitro, following serum stimulation of starved U87MG cells, the expression of FBP1 was upregulated, as well as c-Myc and PCNA. Moreover, knockdown of FBP1 by siRNA transfection diminished the expression of c-Myc and arrested cell growth at G1 phase. Collectively, our results shows that the expression of FBP1 is in close correlation with c-Myc level and cell proliferation in glioma and provides a potential strategy to develop FBP1 inhibitors as novel anti-tumor agents.
Background Human hepatocellular carcinoma (HCC) is one of the most common fatal cancers and an important health problem worldwide, but its mechanism is still unclear. Microtubule (MT) kinesin motor proteins orchestrate a variety of cellular processes (e.g. mitosis, motility and organelle transportation) and have been involved in human carcinogenesis. KIF3B, the kinesin superfamily of proteins (KIFs), plays an important role in the regulation of mitotic progression. Aim The expression of KIF3B and its involvement in HCC was investigated. Methods Western blot and immunohistochemistry were used to measure the expression of KIF3B protein in HCC and adjacent non-tumorous tissues in 57 patients and Cell Counting Kit-8 to analyze the effects of growth and interference of KIF3B in the cell cycle process. Results KIF3B protein level was increased in HCC tissues compared with the adjacent non-tumorous tissues. It was significantly associated with histological differentiation, tumor size, the level of alpha fetal protein (AFP) and proliferation marker Ki-67. Over-expression of KIF3B was correlated with poor survival. Following release of HepG2 cells from serum starvation, the expression of KIF3B was up-regulated. Furthermore, suppression of KIF3B not only decreased cancer cell growth but also induced apoptosis of cells.Conclusions Our results suggested that KIF3B expression was upregulated in HCC tumor tissues and proliferating HCC cells, and an increased KIF3B expression was associated with poor overall survival. KIF3B over-expression is involved in the pathogenesis of hepatocellular carcinoma and may serve as a potential therapeutic target for human HCC.
Nuclear factor of activated T cells 45 kDa (NF45), is a transcription factor that interacts with NF90 to regulate gene expression. It has been proved to be associated with tumor proliferation in various human malignancies. However, the role of NF45 in glioma is poorly understood. The aim of our study was to examine the relationship between NF45 expression and pathological grade in glioma and the impact of NF45 on the proliferation of glioma cells. Expression levels of NF45 are significantly elevated in high-grade human tissue samples compared with low-grade human glioma tissues samples (P < 0.0001) in Western blot analysis. The result of immunohistochemical also revealed that the expression of NF45 was overexpressed in 121 resected gliomas of different pathologic grades and associated with Ki-67. To investigate the role of NF45 in glioma carcinogenesis, we reduced the expression of NF45 by small interfering RNAs, and results showed suppression of cell proliferation, arrest of the cell cycle, and reduction in clone in vitro. Importantly, we show that SiNF45 can induce the expression of p21 and reduce the expression of proliferating cell nuclear antigen (PCNA) and cyclin E. These findings indicate that NF45 plays an important role in the growth regulation of glioma cells, suggesting that NF45 maybe a molecular marker for pathology and a novel therapeutic target for malignant glioma.
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