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Ninjurin2 overexpression promotes glioma cell growth.

ABSTRACT: Ninjurin2 (Ninj2) is an adhesion protein expressed in neurons and glial cells. The current study tested its expression and potential functions in human glioma. We show that Ninj2 mRNA and protein levels are significantly upregulated in human glioma cells and tissues. In established and primary human glioma cells, Ninj2 shRNA or knockout (by CRISPR/Cas9 gene editing) potently inhibited cell survival, growth, proliferation, cell migration and invasion, while inducing apoptosis activation. Contrarily, ectopic overexpression of Ninj2 promoted glioma cell progression in vitro. In human glioma tissues and cells, Ninj2 co-immunoprecipitated with multiple receptor tyrosine kinases (EGFR, PDGFR? and FGFR), required for downstream Akt and Erk activation. Akt and Erk activation was potently inhibited by Ninj2 shRNA or knockout, but enhanced with ectopic Ninj2 overexpression in glioma cells. In summary, we show that Ninj2 overexpression promotes glioma cell growth.

SUBMITTER: Zhou LN

PROVIDER: S-EPMC6932907 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Ninjurin2 overexpression promotes glioma cell growth.

Zhou Li-Na LN Li Ping P Cai Shang S Li Gang G Liu Fang F

Aging 20191202 23

Ninjurin2 (Ninj2) is an adhesion protein expressed in neurons and glial cells. The current study tested its expression and potential functions in human glioma. We show that <i>Ninj2 mRNA</i> and protein levels are significantly upregulated in human glioma cells and tissues. In established and primary human glioma cells, Ninj2 shRNA or knockout (by CRISPR/Cas9 gene editing) potently inhibited cell survival, growth, proliferation, cell migration and invasion, while inducing apoptosis activation. C ...[more]

PMID: 31794427

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Project description:Background: Secreted protein acidic and rich in cysteine (SPARC) plays an important role in cancer development. The roles of SPARC in the liver hepatocellular carcinoma (LIHC) are unclear. Methods: GEPIA2 and UALCAN were used to analyze the SPARC mRNA expression levels in LIHC based on the TCGA database. The GEO database was used to verify the analysis results. Immunohistochemical (IHC) analysis was used to investigate the SPARC protein levels in LIHC tissues. The Kaplan-Meier (KM) plotter was used to analyze the correlation between SPARC and prognosis. The serum SPARC levels were measured by ELISA. CCK8 and murine xenograft models were used to investigate the effect of SPARC on the liver cancer growth in vitro and in vivo. SPARC-correlated genes were screened by LinkedOmics. Results: Based on the TCGA and GEO databases, the analysis showed that the SPARC mRNA expression levels were increased in tumor tissues and peripheral blood mononuclear cell (PBMC) from LIHC compared to normal controls. The IHC analysis showed an increased level of SPARC in LIHC tissues compared to adjacent non-tumor tissues. However, we found that the serum SPARC levels were lower in LIHC than those in healthy controls. The KM plotter showed that there was no significant correlation between the SPARC mRNA levels and overall survival. However, in sorafenib-treated LIHC patients, the high SPARC expression predicts favorable prognosis. Furthermore, the endogenous SPARC overexpression promotes liver cancer cell proliferation in vitro and tumor growth in vivo, while there was no significant effect of exogenous SPARC treatment on liver cancer cell proliferation. Function enrichment analysis of SPARC-correlated genes indicated a critical role of interaction with an extracellular matrix in SPARC-promoting cancer cell proliferation. Conclusion: SPARC mRNAs were increased in LIHC tumor tissues, and SPARC overexpression may promote the liver cancer growth. Further studies are needed to clarify the potential prognostic value of SPARC, both in tissues and in circulation.

Dataset Information

Ninjurin2 overexpression promotes glioma cell growth.

Publications

Ninjurin2 overexpression promotes glioma cell growth.

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