Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin

Abstract

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, Human cervical cancer proto-oncogene (HCCR) aberrantly expressed in a number of malignant tumors, including HCC. HCC is associated with Hepatitis B virus (HBV) infection in a large percentage of cases. To explore the regulation and function of HCCR expression in the development of HCC, we detected HCCR expression in HBV expressing hepatocytes. Results showed that the expression of HCCR was higher in HBV-expressing hepatocytes than that in control cells. Examining different components of HBV revealed that the HBx promotes HCCR expression in hepatocytes via the T-cell factor (TCF)/β-catenin pathway. HCCR expression in HBx transgenic mice increased with as the mice aged and developed tumors. We also found that overexpression of HCCR in hepatocytes promoted cell proliferation, migration, and invasion and reduced cell adhesion. Suppressing HCCR expression abolished the effect of HBx-induced hepatocyte growth. In addition, HCCR represses the expression of E-cadherin by inhibition its promoter activity, which might correlate with the effects of HCCR in hepatocytes. Taken together, these results demonstrate that HBx-HCCR-E-cadherin regulation pathway might play an important role in HBV-induced hepatocarcinogenesis. They also imply that HCCR is a potential risk marker for HCC and/or a potential therapeutic target.

Downregulated exosomal microRNA-148b-3p in cancer associated fibroblasts enhance chemosensitivity of bladder cancer cells by downregulating the Wnt/β-catenin pathway and upregulating PTEN

“…It has also been found that bladder cancer cell-derived exosomes can induce cell proliferation and inhibit tumor cell apoptosis in vitro in conjunction with upregulated expression levels of Bcl-2, but reduced expression levels of Bax and caspase-3 [ 29 ], which is in line with our current observations. Vimentin is a well-recognized metastasis marker [ 30 ], while E-cadherin is known to repress the invasion and metastasis of epithelial cells [ 31 ]. Additionally, CAF-secreted exosomes have been found to reinforce metastasis and chemoresistance by enhancing EMT in colorectal cancer cells [ 7 ].…”

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

“…vimentin expression is a late event in EMT and is preceded by a loss of epithelial features, which leads to the upregulation of mesenchymal genes [45]. E-cadherin, which promotes cell-cell contact and suppresses the malignant invasion and metastasis of epithelial cells, is associated with the invasiveness of HCC cells [46]. The loss of E-cadherin enables metastasis by disrupting intercellular contacts, an early step in metastatic dissemination [29].…”

Ultrasound Microbubble-Mediated microRNA-505 Regulates Cervical Cancer Cell Growth via AKT2

“…The EMT is a crucial mechanism of tumor cell invasion and cancer metastasis, by which epithelial cells obtain mesenchymal fibroblast-like properties [ 35 ]. Vimentin is a well-recognized metastasis marker [ 36 ], while E-cadherin could repress the invasion and metastasis of epithelial cells [ 37 ]. EMT is a great contributor to the CC cell chemotherapy and radiotherapy resistance; thus, inhibiting EMT improves the survival rate of CC patients by sensitizing the CC cells to radiotherapy and drugs [ 32 ].…”