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Neuropeptide Y1 receptor inhibits cell growth through inactivating mitogen-activated protein kinase signal pathway in human hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers, and its incidence is increasing worldwide. Neuropeptide Y (NPY) broadly expressed in the central and peripheral nervous system. It participates in multiple physiological and pathological processes through specific receptors. Evidences are accumulating that NPY is involved in development and progression in neuro- or endocrine-related cancers. However, little is known about the potential roles and underlying mechanisms of NPY receptors in HCC. In this study, we analyzed the expression of NPY receptors by real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Correlation between NPY1R levels and clinicopathological characteristics, and survival of HCC patients were explored, respectively. Cell proliferation was researched by CCK-8 in vitro, and tumor growth was studied by nude mice xenografts in vivo. We found that mRNA and protein level of NPY receptor Y1 subtype (NPY1R) significantly decreased in HCC tissues. Low expression of NPY1R closely correlated with poor prognosis in HCC patients. Proliferation of HCC cells was significantly inhibited by recombinant NPY protein in vitro. This inhibitory effect could be blocked by selected NPY1R antagonist BIBP3226. Furthermore, overexpression of NPY1R could significantly inhibit HCC cell proliferation. Knockdown of NPY1R promoted cell multiplication in vitro and increased tumorigenicity and tumor growth in vivo. NPY1R was found to participate in the inhibition of cell proliferation via inactivating mitogen-activated protein kinase signal pathway in HCC cells. Collectively, NPY1R plays an inhibitory role in tumor growth and may be a promising therapeutic target for HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

NPY:

Neuropeptide Y

PPY:

Pancreatic polypeptide

PYY:

Peptide YY

NPY1R:

Neuropeptide Y receptor Y1 subtype

NPY2R:

Neuropeptide Y receptor Y2 subtype

NPY5R:

Neuropeptide Y receptor Y5 subtype

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-regulated kinase

JNK:

C-Jun N-terminal kinase

TNM stage:

Tumor-node-metastasis stage

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Acknowledgments

This work was funded by the National Natural Science Foundation of China (Nos. 81502100, 81402024), China Postdoctoral Science Foundation (2016M591896), Jiangsu government scholarship for overseas studies, the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Natural Science Foundation of Jiangsu Province, China (BK20140437).

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Authors and Affiliations

  1. Basic Medical Research Centre in Medical College of Nantong University, Nantong, China

    Xiufang Lv, Fengbo Zhao, Baoying Hu, Xiu Gong, Juan Yang & Wenxin Qin

  2. Department of General Surgery, The Affiliated Hospital, Nantong University, Nantong, China

    Weidong Tang

  3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/2200, Xietu Road, Shanghai, 200032, China

    Xisong Huo, Qiujin Shen & Wenxin Qin

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  1. Xiufang Lv
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Lv, X., Zhao, F., Huo, X. et al. Neuropeptide Y1 receptor inhibits cell growth through inactivating mitogen-activated protein kinase signal pathway in human hepatocellular carcinoma. Med Oncol 33, 70 (2016). https://doi.org/10.1007/s12032-016-0785-1

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