Increased expression of OCT4 is associated with low differentiation and tumor recurrence in human hepatocellular carcinoma.

Octamer binding transcription factor 4 (OCT4), a key transcription factor required to maintain self-renewal and pluripotency of human and mouse embryonic stem cells, has been recently identified to be associated with tumorigenesis and malignant transformation of many types of cancers. This study was to determine the roles of OCT4 in HCC recurrence and their impact on the clinical outcome of HCC patients. Western blot and immunohistochemical stains were used to detect the expression of OCT4 protein in 152 HCC tissues and 40 cirrhosis tissues, as well as in 6 human HCC cell lines and normal hepatocytes. OCT4 expression in HCC cell lines and tumor tissues was higher than in normal hepatocytes and cirrhosis tissues. Overexpression of OCT4 was significantly associated with low differentiation and tumor recurrence. Patients with elevated expression of OCT4 protein usually carried a poor overall survival and high recurrence rate. Multivariate analysis showed that OCT4 expression was an independent predictive factor for HCC patients survival. OCT4 might serve as a promising biomarker for the diagnosis of highly recurrent cases of HCC and could be used as a valuable indicator for predicting the prognosis of HCC.

Down-regulation of RhoE is associated with progression and poor prognosis in hepatocellular carcinoma.

BACKGROUND: RhoE is an atypical member of Rho GTPases family, which is a crucial regulator of cytoskeletal dynamics, cell cycle progression, and cell proliferation. Previous studies have reported that RhoE was aberrantly expressed in several human cancers, but the role of RhoE in hepatocellular carcinoma (HCC) remained poor understood. OBJECTIVES: This study investigated the expression of RhoE and its clinical significance on the outcome of patients with HCC. METHODS: The expression of RhoE was examined in HCC patients and then the prognostic impact of the RhoE expression status was evaluated by univariate and multivariate analysis. RESULTS: RhoE was down-regulated in HCC cell lines and tissues compared with normal hepatocyte line (HL-7702) and non-cancerous liver tissues. The expression of RhoE was significantly negatively associated with serum AFP (P = 0.013) and tumor grade (P = 0.016). Furthermore, the patients with low expression of RhoE had a shorter survival (P = 0.002) than those with high expression. Univariate and multivariate analysis showed that RhoE expression was a significant and independent prognostic predictor for HCC patients (P = 0.016). CONCLUSIONS: RhoE, down-regulated in patients with HCC, could serve as an independent prognostic predictor for patients with HCC.

Up-regulated miR-17 promotes cell proliferation, tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma.

Emerging evidence indicates that the miR-17 family may have a causal role in human cancer tumorigenesis, but their specific effects on the occurrence of CRC (colorectal carcinoma) are still poorly understood. In the present study, we profiled CRC tissue samples by miRNA (microRNA) microarray and found that four members of the miR-17 family had higher expression in CRC tissues than in normal tissues. This finding was further validated by qRT-PCR (quantitative reverse transcription PCR). Transfecting CRC cells with an inhibitor of miR-17 lowered their ability to proliferate and induced G0/G1 arrest. We also confirmed that miR-17 exerted this function by directly targeting RND3 in vitro, and that the expression of miR-17 was negatively correlated with that of RND3 in CRC tissues and CRC cells. Moreover, miR-17 inhibition led to tumour growth suppression and up-regulation of RND3 expression in a nude mouse xenograft model. RND3 expression was found to be significantly lower in CRC tissues than in normal tissues and adenomas, indicating that RND3 may act as a tumour suppressor gene in CRC. In conclusion, the present study suggests that miR-17 plays an important role in CRC carcinogenesis by targeting RND3 and may be a therapeutic agent for CRC.

Protein kinase CK2α is overexpressed in colorectal cancer and modulates cell proliferation and invasion via regulating EMT-related genes.

BACKGROUND: Protein kinase CK2 is a highly conserved, ubiquitous protein serine/threonine kinase that phosphorylates many substrates and has a global role in numerous biological and pathological processes. Overexpression of the protein kinase CK2α subunit (CK2α) has been associated with the malignant transformation of several tissues, with not nearly as much focus on the role of CK2α in colorectal cancer (CRC). The aims of this study are to investigate the function and regulatory mechanism of CK2α in CRC development. METHODS: Expression levels of CK2α were analyzed in 144 patients (104 with CRC and 40 with colorectal adenoma) by immunohistochemistry. Proliferation, senescence, motility and invasion assays as well as immunofluorescence staining and western blots were performed to assess the effect of CK2α in CRC. RESULTS: The immunohistochemical expression of nuclear CK2α was stronger in tumor tissues than in adenomas and normal colorectal tissues. Suppression of CK2α by small-interfering RNA or the CK2α activity inhibitor emodin inhibited proliferation of CRC cells, caused G0/G1 phase arrest, induced cell senescence, elevated the expression of p53/p21 and decreased the expression of C-myc. We also found that knockdown of CK2α suppressed cell motility and invasion. Significantly, CK2α inhibition resulted in ß-catenin transactivation, decreased the expression levels of vimentin and the transcription factors snail1 and smad2/3, and increased the expression of E-cadherin, suggesting that CK2α regulates the epithelial-mesenchymal transition (EMT) process in cancer cells. CONCLUSIONS: Our results indicate that CK2α plays an essential role in the development of CRC, and inhibition of CK2α may serve as a promising therapeutic strategy for human CRC.

[Correlation of casein kinase 2ß overexpression to the metastatic ability of colorectal cancer cells in vitro].

OBJECTIVE: To investigate the expression of casein kinase 2ß (ck2ß) in colorectal cancer in relation to the metastatic ability of the cancer cells. METHODS: The expression of ck2ß in 46 normal colorectal mucosa, 20 colorectal adenomas and 66 colorectal cancers were detected immunohistochemically. In colorectal cancer cells, Ck2ß protein expression was knockdown by RNA interference using ck2ß-specific small interfering RNA (siRNA) and the interference efficiency was assessed by Western blotting. The effect of ck2ß gene knockdown on the proliferation of the colorectal cancer cells was tested with colony formation assay, and the changes in the invasive ability of the cells were observed using Transwell chamber assay. RESULTS: Negative or weak ck2ß expression was detected in normal colorectal mucosa, with nuclear positivity in 8.7% and cytoplasmic positivity in 13.0% of the cases. Colorectal adenomas showed moderate ck2ß expression, with 60% cases showing positivity in the cell nuclei and 40% in the cytoplasm. In colorectal cancers, significantly stronger expression of ck2ß was found than that in colorectal adenomas and normal colorectal mucosa (P<0.05), and 75.8% cases showed positivity in the cell nuclei and 62.1% showed cytoplasmic positivity; the expression of ck2ß protein in colorectal cancers with lymph node metastasis was even higher (P<0.05). Ck2ß knockdown obviously inhibited the proliferation and invasiveness of colorectal cancer cells in vitro. CONCLUSION: The high expression of ck2ß in colorectal cancer is closely correlated to the carcinogenesis and metastasis of the tumor.

[Effect of protein kinase CK2 gene silencing on radiosensitization in human nasopharyngeal carcinoma cells].

OBJECTIVE: To investigate the effect of protein kinase CK2 gene silencing on the radiosensitization in human nasopharyngeal carcinoma (NPC) cells and its possible mechanism. METHODS: RNA interference (RNAi) technique was used to down-regulate the protein kinase CK2alpha expression in 5-8F cells, and clonogenic assay was employed to observe the changes in the radiosensitivity of the cells. DNA double-strand break was assessed by immunofluorescence staining of gamma-H2AX foci, and the cell apoptosis was examined using Annexin V-FITC/PI double-staining flow cytometry. RESULTS: CK2alpha protein was successfully silenced by siRNA. CK2alpha knockdown significantly decreased the clonogenic activity and increased the radiosensitivity of the NPC cells. After a 15-min exposure of the cells to 1 Gy radiation, significant difference occurred in the gamma-H2AX foci between CK2alpha knockdown cells and the control cells (P<0.01). CK2alpha silencing significantly increased the cell apoptosis after the exposure (P<0.01). CONCLUSIONS: Protein kinase CK2 plays an important role in the radiosensitivity of the NPC cells, and suppression of its expression might be a potential therapeutic approach of cancer.