Hepatocellular carcinoma (HCC) has a poor prognosis, owing to its high potential for growth and metastasis. In this study, we aimed to investigate the roles of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP)in human HCCcell growth and metastasis. We analyzed the LHPP expression level in human HCC tissues paired normal tissues in the Oncomine database, and assessed the relationship between the LHPP expression levels with HCC patient’s overall survival and the prognostic value of LHPP in human HCC by Kaplan-Meier survival analysis. Real-time PCR and Western Blot were used to examine the expression levels of LHPP in normal liver cell line (LO2) and human HCC cell lines (SMCC-7721, HepG2, Huh7, MHCC-97 H, and LM3). Through lentivirus infection, we established human HCC stable cell lines (Huh7 and LM3) overexpressing LHPP. Then, we detected these cell viability, colony , and invasion. Subsequently, we performed the gene set enrichment analysis (GSEA) for the RNA-seq data of HCC patients from TCGA. Finally, we examined the expression level of several oncogenes, including CCNB1, PKM2, MMP7, and MMP9, in these cells via real-time PCR assay. Here, we found thatLHPPis significantly downregulated in the human HCC tissues paired normal tissues. Furthermore, the high expression level of LHPP is associated with better clinical outcomes in human HCC. Overexpression of LHPPinhibitscell growth and metastasis in human HCC cells, and LHPP expression levels negatively correlate with cell cycle and metastasis in HCC tissues. Moreover, the level of LHPP is negatively correlated with CCNB1, PKM2, MMP7, and MMP9 in human HCC cells and HCC tissues. These findings highlight a novel tumor suppressor in human HCC growth and metastasis, and provide a promising diagnostic and prognostic factor for humanHCC.

肝细胞癌（HCC）由于其生长和转移的高潜力而预后不良。在这项研究中，我们旨在研究磷酸赖氨酸磷酸组氨酸无机焦磷酸磷酸酶 (LHPP)在人 HCC 细胞生长和转移中的作用。我们分析了LHPP在Oncomine数据库配对正常组织人肝癌组织中的表达水平，并评估了关系LHPP与肝癌患者的总生存期及预后价值的表达水平LHPP在肝癌采用Kaplan-Meier生存分析。Real-time PCR 和 Western Blot 检测LHPP的表达水平在正常肝细胞系 (LO2) 和人类 HCC 细胞系（SMCC-7721、HepG2、Huh7、MHCC-97 H 和 LM3）中。通过慢病毒感染，我们建立了过表达LHPP 的人 HCC 稳定细胞系（Huh7 和 LM3）。然后，我们检测了这些细胞活力、集落和侵袭。随后，我们对来自 TCGA 的 HCC 患者的 RNA-seq 数据进行了基因集富集分析 (GSEA)。最后，我们通过实时 PCR 测定检测了这些细胞中几种致癌基因的表达水平，包括 CCNB1、PKM2、MMP7 和 MMP9。在这里，我们发现LHPP在与正常组织配对的人类 HCC 组织中显着下调。此外，LHPP的高表达水平与人类 HCC 更好的临床结果相关。过度表达LHPP抑制人 HCC 细胞的细胞生长和转移，LHPP表达水平与 HCC 组织中的细胞周期和转移呈负相关。此外，LHPP的水平与人 HCC 细胞和 HCC 组织中的 CCNB1、PKM2、MMP7 和 MMP9 呈负相关。这些发现突出了人类 HCC 生长和转移中的一种新型肿瘤抑制因子，并为人类 HCC 提供了一个有希望的诊断和预后因素。