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Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration.

ABSTRACT: Pregnancy zone protein (PZP), a member of the proteinase inhibitor I39 (-2-macroglobulin) family of proteins, is involved in the initiation and development of various tumors. The gene encoding PZP is hypermethylated and expressed at low levels in hepatocellular carcinoma (HCC) tissue and cells, but the function of PZP in HCC cells remains unclear. Here, we analyzed DNA methylation and mRNA expression of HCC in The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset. We identified 10 methylation-driven genes, of which PZP was significantly hypermethylated and poorly expressed in tumor tissue. We confirmed that PZP is highly methylated and poorly expressed in HCC cell lines via quantitative real-time PCR experiment and methylation-specific PCR. Furthermore, PZP markedly inhibited the proliferation, invasion and migration of HCC cells. These findings may provide a basis for exploring novel therapeutic targets for HCC.

SUBMITTER: Wu M

PROVIDER: S-EPMC7931217 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration.

Wu Minhua M Lan Hui H Ye Zhongwei Z Wang Yonghui Y

FEBS open bio 20210221 3

Pregnancy zone protein (PZP), a member of the proteinase inhibitor I39 (-2-macroglobulin) family of proteins, is involved in the initiation and development of various tumors. The gene encoding PZP is hypermethylated and expressed at low levels in hepatocellular carcinoma (HCC) tissue and cells, but the function of PZP in HCC cells remains unclear. Here, we analyzed DNA methylation and mRNA expression of HCC in The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset. We identified 10 methy ...[more]

PMID: 33471436

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Project description:Septin 6 (SEPT6) is a member of the GTP‑binding protein family that is highly conserved in eukaryotes and regulates various biological functions, including filament dynamics, cytokinesis and cell migration. However, the functional importance of SEPT6 in hepatocellular carcinoma (HCC) is not completely understood. The present study aimed to investigate the expression levels and roles of SEPT6 in HCC, as well as the underlying mechanisms. The reverse transcription quantitative PCR, western blotting and immunohistochemistry staining results demonstrated that SEPT6 expression was significantly elevated in HCC tissues compared with corresponding adjacent non‑tumor tissues, which indicated that SEPT6 expression may serve as a marker of poor prognosis for HCC. By performing plasmid transfection and G418 treatment, stable SEPT6‑knockdown and SEPT6‑overexpression cell lines were established. The Cell Counting Kit‑8, flow cytometry and Transwell assay results demonstrated that SEPT6 overexpression significantly increased HCC cell proliferation, cell cycle transition, migration and invasion compared with the Vector group, whereas SEPT6 knockdown displayed significant suppressive effects on HCC cell lines in vitro compared with the control group. Mechanistically, SEPT6 might facilitate F‑actin formation, which induced large tumor suppressor kinase 1 dephosphorylation, inhibited Hippo signaling, upregulated yes‑associated protein (YAP) expression and nuclear translocation, and upregulated cyclin D1 and matrix metallopeptidase 2 (MMP2) expression. Furthermore, YAP overexpression significantly reversed SEPT6 knockdown‑induced inhibitory effects on HCC, whereas YAP knockdown significantly inhibited the oncogenic effect of SEPT6 overexpression on HCC. Collectively, the present study demonstrated that SEPT6 may promote HCC progression by enhancing YAP activation, suggesting that targeting SEPT6 may serve as a novel therapeutic strategy for HCC.

Dataset Information

Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration.

Publications

Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration.

Similar Datasets

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