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Oncology reports

BCL-3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.


PMID 26882953

Abstract

Previous studies have demonstrated the aberrant expression and oncogenic role of B-cell CLL/lymphoma-3 (BCL-3) in human malignancies. However, the clinical significance of BCL-3 and its biological function in human hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression levels of BCL-3 protein and mRNA in 90 pairs of HCC and matched non-tumor tissues were analyzed using immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We found that the expression levels of BCL-3 protein and mRNA in HCC tissues were significantly higher than those in the matched tumor-adjacent tissues. In addition, positive expression of BCL-3 was associated with adverse clinicopathological characteristics of the HCC patients including hepatitis B virus (HBV) infection, tumor size, cirrhosis and advanced tumor-node-metastasis (TNM) stage. Moreover, HCC patients with positive expression of BCL-3 had significantly decreased 5-year overall survival and recurrence-free survival. Importantly, BCL-3 expression was an independent prognostic factor for indicating the survival of the HCC patients. Functionally, BCL-3 knockdown markedly inhibited cell viability, proliferation and cell cycle progression in HepG2 cells, while BCL-3 overexpression promoted these cellular processes in Huh7 cells. Accordingly, in vivo experiments indicated that BCL-3 knockdown prominently suppressed the tumor growth of HepG2 cells in nude mice. Mechanistically, we revealed that the expression of cyclin D1 was decreased after BCL-3 knockdown in the HepG2 cells and was increased after BCL-3 overexpression in the Huh7 cells. Cyclin D1 silencing was found to abrogate the functional effects of BCL-3 on cellular processes in Huh7 cells. Taken together, our data suggest that BCL-3 may serve as a promising biomarker and an effective therapeutic target of HCC.

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EHU054231 MISSION® esiRNA, esiRNA human BCL3 (esiRNA1)