Zheng Mo, Minggen Hu, Fei Yu, Lijuan Shao, Kexing Fan, Shunchang Jiao

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. The objective of this study was to investigate expression pattern and biological roles of LRP16 in pancreatic cancer. 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. 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. These findings suggest that LRP16 played an oncogenic role in pancreatic carcinoma.