Proliferation inhibition and differentiation induction of hepatic cancer stem cells by knockdown of BC047440: A potential therapeutic target of stem cell treatment for hepatocellular carcinoma
Recent findings suggest that clinical hepatocellular carcinoma (HCC) progression is driven by hepatic cancer stem cells (HCSCs) through their capacity for self-renewal, generation of heterogeneous lineages of cancer cells, resistance to chemotherapy and their ability to divide limitlessly,
which may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, HCSC-directed therapeutic approaches might represent strategies to improve clinical HCC therapy. In previous studies, we showed that BC047440 was found to play a critical role in
mediating HCC cell proliferation. The present study sought to determine whether BC047440 is involved in maintaining HCSC malignant behavior (including proliferation and differentiation). We demonstrated that BC047440 expression was markedly upregulated in HCSCs. Furthermore, we inhibited BC047440
in HCSCs using short hairpin RNA (shRNA). The effects of BC047440 on proliferation and differentiation were investigated. We also analyzed the involvement of critical molecular events known to regulate the proliferation and the differentiation machinery. Excluding apoptosis-related effects,
we found that BC047440 inhibition resulted in enhanced cell proliferation through enhancing cytoplasmic accumulation of nuclear factor-κB (NF-κB) with a concomitant decrease in the nuclear fraction. BC047440 inhibition also resulted in inducing HCSC differentiation into hepatocytes.
Furthermore, following downregulation of BC047440, the level of hepatocyte nuclear factor 4α (HNF4α) increased. Finally, tumorigenicity suppression following BC047440 depletion was confirmed in a nude mouse model. In conclusion, our findings indicate that BC047440 plays an important
role in the proliferation and differentiation of HCSCs and may represent a novel therapeutic target for the treatment of HCC.
Document Type: Research Article
Affiliations: 1: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China 2: PLA Center of General Surgery, General Hospital of Chengdu Army Region, Chengdu, Sichuan 610083, P.R. China 3: Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Publication date: 01 January 2014
- Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
The journal is published in both print and electronic format. - Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites
- Access Key
- Free content
- Partial Free content
- New content
- Open access content
- Partial Open access content
- Subscribed content
- Partial Subscribed content
- Free trial content