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Leukemia-related protein 16 (LRP16) promotes tumor growth and metastasis in pancreatic cancer

Authors Mo Z, Hu MG, Yu F, Shao LJ, Fan KX, Jiao SC

Received 23 November 2017

Accepted for publication 16 January 2018

Published 5 March 2018 Volume 2018:11 Pages 1215—1222

DOI https://doi.org/10.2147/OTT.S157914

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza


Zheng Mo,1,* Minggen Hu,1,* Fei Yu,2 Lijuan Shao,1 Kexing Fan,1,3 Shunchang Jiao1

1PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 3International Joint Cancer Institute, The Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Background: Leukemia related protein 16 (LRP16), one of the genes belonging to the macro domain family, has been found up-regulated in various tumors including testicles, ovaries and mucosa of colon and is associated with poor clinical outcomes.
Purpose: The objective of this study was to investigate expression pattern and biological roles of LRP16 in pancreatic cancer.
Patients and methods: Western blot and immunohistochemistry were used to investigate the expression of LRP16 in pancreatic cancer cell lines and tissues. qRT-PCR was utilized to examine LRP16 mRNA expression. Lentivirus based overexpression and knockdown of LRP16 was carried out in four pancreatic cancer cell lines (Panc1, CFPAC1, SW1990 and AsPC1). Cell proliferation, migration and invasion were determined by MTS and transwell assay, respectively. Flow cytometry was performed to investigate cell apoptosis. In vivo, the tumorigenic ability of LRP16 was determined in a NOD/SCID mouse model.
Results: In the present study, we found that LRP16 expression was increased in pancreatic tumor samples, compared with normal tissues. Moreover, the LRP16 expression was positive in 60.9% of 156 specimens and correlated with tumor size, clinical stage, distant metastasis and tumor differentiation. Multivariate Cox regression analysis revealed that the level of LRP16 expression was an independent prognostic factor for overall survival in pancreatic cancer patients. Furthermore, silencing of LRP16 significantly accelerated apoptosis, decrease proliferation, migration and invasion of pancreatic cancer cell lines in vitro. In contrast, overexpression of LRP16 attenuated apoptosis, promoted proliferation, migration and invasion. In addition, in vivo study revealed that down regulation of LRP16 could attenuate tumor growth and prolong the survival. On the contrary, up-regulation of LRP16 could promote tumor growth and shorten their survival.
Conclusion: These findings suggest that LRP16 played an oncogenic role in pancreatic carcinoma.

Keywords:
leukemia-related protein 16, pancreatic cancer, proliferation, metastasis

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