Tumor Suppressor LHPP Suppresses Cell Proliferation and Epithelial-mesenchymal Transition in Hepatocellular Carcinoma Cell Lines

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in the world with high mortality due to its high potential of metastasis. Epithelial-mesenchymal transition (EMT) plays a key role in the pathogenesis of HCC occurrence and metastasis. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. There is little study about LHPP in human HCC development. In the present study, we aimed to investigate the role of LHPP in human HCC cell metastasis. We analyzed the LHPP expression level in human HCC tissues compared with normal tissues in the public database. We detected the mRNA level and protein level of LHPP in transformed liver cell line (LO2) and human HCC cell lines (MHCC-97 H, MHCC-97L, and HepG2). We performed genetic gain and loss of function experiments with LHPP using small interfering RNA (siRNA) and lentivirus infection. Then, we detected that LHPP suppressed proliferation and promoted apoptosis in hepatocellular carcinoma cell lines. Also, we investigated the role of LHPP in the EMT process. Finally, we examined the effect of LHPP on TGF-β-induced EMT. Interestingly, we also found that LHPP expression is positively regulated tumor suppressor p53. Our data showed that LHPP is significantly decreased in the human HCC tissues and human HCC cell lines compared with normal liver tissues and transformed liver cells. Knockdown of LHPP promotes HCC cell proliferation and metastasis, and LHPP expression levels negatively correlate with EMT-related genes. Furthermore, LHPP inhibits TGF-β-induced EMT in HCC cell lines. These studies validate LHPP as a tumor suppressor in liver cancer and provide a new genetic target for HCC diagnosis and treatment.