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.
C-Terminal EH domain-containing protein 2 (EHD2) of the EHD family is associated with plasma membrane. We investigated the expression of EHD2 in human esophageal squamous cell carcinoma (ESCC) and the EHD2 expression to study the therapeutic effect of chemotherapy drugs. Western blot and immunohistochemistry were used to measure the expression of EHD2 protein in ESCC and adjacent normal tissue in 98 patients. EHD2 protein level was reduced in ESCC tissues in comparison with adjacent normal tissues. Under-expression of EHD2 increased the motility property of ESCC cell TE1 in vitro by wound-healing assays and transwell migration assays, and it was concurrent with the decreased expression of epithelial marker E-cadherin. Under-expression of EHD2 in TE1 can cause resistance to cisplatin. Our results suggested that EHD2 low expression is involved in the pathogenesis of ESCC, and it might be a favorable independent poor prognostic parameter for ESCC.
We can conclude that CCNH and CDK7 may play an important role in the tumorigenesis and development of ESCC. CCNH and CDK7 expression affected the chemotherapy of tumor.
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