Targeting ZBP-89 for the treatment of hepatocellular carcinoma

ABSTRACT

Introduction: Zinc-binding protein-89 (ZBP-89) is a Krüppel-type zinc-finger transcription factor that regulates target gene expression profiles via directly binding to GC-rich gene promoters, recruiting chromatin modifiers or by interacting with other proteins. The importance of ZBP-89 in the regulation of cell cycle arrest and apoptosis has led to increased interest and investigations for its role in cancer development.

Areas covered: We describe ZBP-89 as a candidate therapeutic target for hepatocellular carcinoma (HCC) from several perspectives. ZBP-89 can upregulate apoptosis in HCC in a p53-dependent or – independent manner. In addition, the negative regulation of ZBP-89 on liver cancer stemness sheds light on its possible effect on sensitizing HCC to chemotherapies and the reduction of HCC relapse. The prognostic significance of ZBP-89 in HCC patients further suggests its clinical importance as a potential tumor suppressor.

Expert opinion: Given the roles of ZBP-89 in HCC, we believe, ZBP-89 is a promising therapeutic target for enhancing apoptosis and diminishing the liver cancer stemness. At the same time, we also face a series of challenges, especially in the clinical implication of ZBP-89. Resolving the current controversies will advance the development of ZBP-89 for anti-HCC therapy.

KEYWORDS:

• Apoptosis
• cancer stemness
• hepatocellular carcinoma
• transcription factor
• ZBP-89

Article highlights

• ZBP-89 functions as a transcription factor to regulate gene expression via multiple mechanisms.

• ZBP-89 have pro-tumor or antitumor roles in different cancer types. In HCC, ZBP-89 is a potential tumor suppressor.

• The higher expression of ZBP-89 predicts better survivals and lower recurrence of HCC patients.

• ZBP-89 upregulates apoptosis in a p53-dependent or -independent manner in HCC cells.

• The negative regulatory effects of ZBP-89 on liver cancer stemness may bring clinical benefits of reduced therapeutic resistance and recurrence.

• Current controversies and issues for the development of ZBP-89 targeted therapies have been stated and need further investigation.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was funded by grants from the Research Grants Council of the Hong Kong Special Administrative Region (No. 14109516), the National Natural Science Foundation of China (No. 81472339) and the Chinese University of Hong Kong (CHUK) (Direct Grant 2015.1.083).