LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling
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Elevated LRP16 expression is associated with poor clinical outcomes in multiple malignancies. We detected LRP16 expression in hepatocellular carcinoma (HCC) and found that it was downregulated in tumor samples and HCC cell lines. In a cohort of 80 HCC patients, high level of LRP16 expression in HCC tumors was associated with well differentiation, less lymph node metastasis, and good overall survival (OS). Overexpression of LRP16 in the HepG2 and MHCC-97L cell lines increased cell apoptosis, attenuated cell proliferation, migration, and invasion ability in vitro, and drastically diminished tumor growth and metastasis in vivo. Silencing LRP16 in HCC-LM3 and SMMC-7721 cell lines showed opposite results. Microarray evaluation of tumor cells overexpressing LRP16 revealed the effects on decreased activity in the Wnt signaling pathway. These results were confirmed by qRT-PCR and Western blots. Furthermore, inhibition of Wnt signaling decreased proliferation, migration, and invasion of HCC cell lines. Mechanism conducted showed that LRP16 overexpression could prevent β-catenin from entering the nucleus. Our study demonstrated that LRP16 suppresses tumor growth in HCC by modulating Wnt/β-catenin signaling.
LRP16 was low expression in HCC tissue and cell lines.
Low expression of LRP16 in HCC was associated with poor prognosis.
LRP16 inhibits activation of the Wnt/β-catenin pathway in HCC.
LRP16 prevents β-catenin from entering the nucleus.
KeywordsLeukemia-related protein 16 Hepatocellular carcinoma Metastasis Wnt/β-catenin signaling
We thank Zizheng Wang at the Hepatological Surgery Department of PLA for his analysis assistance.
This work was supported by grants from the Ministry of Science & Technology (“973” projects) (No. 2012CB917104) and the National Natural Science Foundation of China (No. 81341069; 81172853).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
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