Expression of Tenascin-C in glioma and its effect on temozolomide therapeutic value

doi:10.3877/cma.j.issn.2095-123X.2021.03.002

Abstract

Abstract:

Objective

To investigate the expression characteristics and clinical relevance of Tenascin-C (TNC) in glioma and the effect of TNC on the efficacy of temozolomide (TMZ) in the treatment of glioma.

Methods

The Human Protein Atlas and Chinese Glioma Genome Atlas (CGGA) database were used to evaluate the expression level of TNC in glioma and its clinical significance. TNC shRNA plasmid and overexpression plasmid of TNC, and the related lentivirus were used to inhibit or enhance the expression of TNC protein in U87MG and U251 cells. Cell proliferation and survival were detected by CCK-8 assay, and tumor cells U87MG in situ tumor formation in nude mice, were used to evaluate the effect of TNC on the efficacy of TMZ in the treatment of glioma.

Results

(1)The Human Protein Atlas database showed that TNC was not expressed or low expressed in normal nerve cells, and was highly expressed in glioma cells (U138MG, U87MG, U251). (2)In the CGGA database, the transcription level of TNC in WHO grade Ⅳ glioblastoma was significantly higher than that in WHO grade Ⅱ and WHO grade Ⅲ glioblastoma (P<0.05). The mRNA level of TNC in IDH wild-type glioma was significantly higher than that in IDH mutant glioma (P<0.05), as well as significantly higher in patients without 1P/19q combined deletion glioma than 1P/19q combined deletion glioma (P<0.05). Patients with high TNC mRNA levels had significantly shorter survival outcomes (17.33 months) compared with those with low TNC mRNA levels (89.87 months) (P<0.05). (3)TNC overexpression significantly reduced the proliferation inhibition and tumor killing effect of TMZ on U87MG and U251 cells (P<0.05), and interference with TNC expression significantly enhanced the proliferation inhibition and tumor killing effect of TMZ on U87MG and U251 cells (P<0.05). Interfering TNC expression significantly enhanced the inhibitory effect of TMZ on intracranial U87MG in nude mice (P<0.05), and the overexpression of TNC significantly reduced the inhibitory effect of TMZ on intracranial U87MG in nude mice (P<0.05).

Conclusion

TNC is highly expressed in glioma and is negatively correlated with survival prognosis of patients. TNC level significantly regulates the efficacy of TMZ in the treatment of glioma, and inhibition of TNC expression may be an effective means to improve the efficacy of TMZ.

Key words: Glioma, Tenascin-C, Temozolomide

Lu Chen, Qilu Li, Shujun Li. Expression of Tenascin-C in glioma and its effect on temozolomide therapeutic value[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2021, 11(03): 132-138.

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References 19

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