Tumor Biology

, Volume 37, Issue 6, pp 8305–8315 | Cite as

Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma

  • Hongchen Zhang
  • Zhizhen Li
  • Bingfeng Chu
  • Fei Zhang
  • Yijian Zhang
  • Fayong Ke
  • Yuanyuan Chen
  • Yi Xu
  • Shibo Liu
  • Shuai Zhao
  • Haibin Liang
  • Mingzhe Weng
  • Xiangsong Wu
  • Maolan Li
  • Wenguang Wu
  • Zhiwei Quan
  • Yingbin Liu
  • Yong Zhang
  • Wei Gong
Original Article

Abstract

LIM and SH3 protein 1 (LASP-1) is demonstrated to play a key role in occurrence and development of tumors. However, the expression and function of LASP-1 in cholangiocarcinoma (CCA) remain largely unexplored. This study aimed to investigate the effect of regulated LASP-1 expression on migration, invasion, proliferation, and apoptosis of CCA cells and on tumorigenesis in vivo, and to examine clinico-oncological correlates of LASP-1 expression. Expression of LASP-1 by immunohistochemistry was evaluated in CCA tissue samples. HCCC-9810 and RBE cells were transfected with the LASP-1 small interfering RNA (siRNA), and the effect of knocking down LASP-1 gene expression on cell migration, invasion, proliferation, and apoptosis were examined by wound healing, transwell assays, CCK-8 assays, colony formation, and flow cytometry assays, respectively. Xenograft tumor model was used to validate the effect of downregulated LASP-1 in vivo. Our results demonstrated that LASP-1 was over-expressed in CCA tissues, positively correlating with larger tumors, poor histological differentiation, lymph node metastasis, advanced TNM stage, and poor prognosis in CCA patients (P < 0.05). Downregulation of LASP-1 in HCCC-9810 and RBE cell lines significantly increased cell apoptosis and suppressed cell migration, invasion, and proliferation in vitro and tumorigenesis in vivo. Our results indicate that LASP-1 may essentially involve in the metastasis and growth of CCA and clinical significance of LASP-1 may reside in function as a biomarker to predict prognosis and as a promising therapeutic strategy for CCA patients by the inhibition of LASP-1 expression.

Keywords

LASP-1CCA Prognosis Cell migration Cell invasion Cell proliferation Apoptosis 

Notes

Acknowledgments

This study was supported by the Introductory Funding project from Shanghai Science and Technology Bureau (124119a0600) to WG and Science and Technology funding project of Shanghai Jiao Tong University, School of Medicine (13xj22003) to BFC.

Compliance with ethical standards

This study was performed with approval of the Ethics Committee of Xinhua Hospital and the ethical guidelines of the Declaration of Helsinki. In addition, written informed consent was obtained from all participants.

All experimental procedures were approved by the Institutional Animal Care and Use Committee of Shanghai Jiao Tong University (Shanghai, China).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Hongchen Zhang
    • 1
    • 2
  • Zhizhen Li
    • 1
    • 2
  • Bingfeng Chu
    • 1
    • 2
  • Fei Zhang
    • 1
    • 2
  • Yijian Zhang
    • 1
    • 2
  • Fayong Ke
    • 1
    • 2
  • Yuanyuan Chen
    • 1
    • 2
  • Yi Xu
    • 1
    • 2
  • Shibo Liu
    • 1
    • 2
  • Shuai Zhao
    • 1
    • 2
  • Haibin Liang
    • 1
    • 2
  • Mingzhe Weng
    • 1
    • 2
  • Xiangsong Wu
    • 1
    • 2
  • Maolan Li
    • 1
    • 2
  • Wenguang Wu
    • 1
    • 2
  • Zhiwei Quan
    • 1
    • 2
  • Yingbin Liu
    • 1
    • 2
  • Yong Zhang
    • 1
    • 2
  • Wei Gong
    • 1
    • 2
  1. 1.Department of General Surgery, Xinhua Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  2. 2.The Institute of Biliary Disease Research, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina

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