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Molecular Medicine

, Volume 18, Issue 3, pp 507–518 | Cite as

Characterization of Bridging Integrator 1 (BIN1) as a Potential Tumor Suppressor and Prognostic Marker in Hepatocellular Carcinoma

  • Ke Pan
  • Xiao-ting Liang
  • Hua-kun Zhang
  • Jing-jing Zhao
  • Dan-dan Wang
  • Jian-jun Li
  • Qizhou Lian
  • Alfred E Chang
  • Qiao Li
  • Jian-chuan Xia
Research Article

Abstract

It has been shown that bridging integrator 1 (BIN1) can interact with c-myelocytomatosis (c-Myc) oncoprotein in cancer. However, the role of BIN1 in hepatocellular carcinoma (HCC) is not clear. In the present study, we investigated the expression and prognostic role of BIN1 in primary HCC and evaluated the function of BIN1 in hepatocarcinogenesis. Using real-time polymerase chain reaction and Western blot analysis, we found significantly decreased expression of BIN1 in primary HCC tumor tissues (n = 42) compared with adjacent normal tissues and in HCC cell lines. Immunohistochemistry analysis also found decreased BIN1 expression in HCC tumor tissues (n = 117). In clinicopathological analysis, loss of BIN1 expression correlated significantly (P < 0.05) with differentiation scores and tumor size. Importantly, decreased expression of BIN1 in tumors was found to be closely associated with a poor prognosis, and we conclude that BIN1 was an independent prognostic factor in a multivariate analysis. In mechanistic studies, restoring BIN1 expression in BIN1-null HCC cells significantly inhibited cell proliferation and colony formation and induced apoptosis of HCC cells. Furthermore, we found that BIN1 overexpression could significantly suppress the motility and invasion of HCC cells in vitro. Our results indicate that BIN1 may function as a potential tumor suppressor and serve as a novel prognostic marker in HCC patients. The BIN1 molecule might play an important role in tumor growth, cell motility and invasion. Modulation of BIN1 expression may lead to clinical applications of this critical molecule in the control of hepatocellular carcinoma as well as in early and effective diagnosis of this aggressive tumor.

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (30973398) and Guangdong Natural Science Foundation (925100890) and was partially supported by the Gillson Longenbaugh Foundation.

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Authors and Affiliations

  • Ke Pan
    • 1
  • Xiao-ting Liang
    • 1
    • 2
  • Hua-kun Zhang
    • 1
    • 3
  • Jing-jing Zhao
    • 1
  • Dan-dan Wang
    • 1
  • Jian-jun Li
    • 1
  • Qizhou Lian
    • 2
  • Alfred E Chang
    • 4
  • Qiao Li
    • 4
  • Jian-chuan Xia
    • 1
  1. 1.State Key Laboratory of Oncology in Southern China and Department of Experimental ResearchSun Yat-sen University Cancer CenterGuangzhouChina
  2. 2.Cardiology Division, Department of Medicine, and Research Centre of Heart, Brain, Hormone, and Healthy AgingUniversity of Hong KongPokfulamHong Kong, China
  3. 3.Central Laboratory of Shenzhen Maternity and Child Healthcare HospitalSouthern Medical UniversityShenzhen, GuangdongChina
  4. 4.Department of SurgeryUniversity of Michigan Medical Center, 1520A MSRB-1Ann ArborUSA

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