Circ_0005075 stimulates the proliferation and metastasis of glioma via downregulating SIRT1

D.-Z. Fang, W.-J. Wang, F.-Y. Li, J. Liu, X.-B. Hui, D. Liu, X.-D. Wang

Department of Neurosurgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an, China. wxdxa19800@126.com

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• Oncology

OBJECTIVE: The aim of this study was to uncover the potential influence of circ_0005075 on the malignant progression of glioma and the underlying mechanism.

PATIENTS AND METHODS: Circ_0005075 level in glioma tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relation between circ_0005075 expression and metastasis of glioma patients was analyzed. Prognostic potential of circ_0005075 in glioma was assessed by calculating overall survival (OS) and progression-free survival (PFS). After knockdown or overexpression of circ_0005075, changes in the viability, migration, and wound closure percentage of T98-G and U87 cells were examined, respectively. Subsequently, expression pattern and prognostic value of SIRT1 in glioma patients were determined. Furthermore, the involvement of SIRT1 in glioma progression affected by circ_0005075 was evaluated through rescue experiments.

RESULTS: Circ_0005075 was significantly up-regulated in glioma tissues and cell lines. Meanwhile, its expression level was significantly higher in glioma patients with lymphatic metastasis or distant metastasis when compared with those with negative metastasis. OS and PFS were both remarkably worse in glioma patients with high expression level of circ_0005075. Knockdown of circ_0005075 decreased the viability, migration, and wound closure percentage of T98-G cells. However, overexpression of circ_0005075 in U87 cells yielded the opposite trends. SIRT1 expression level was negatively regulated by circ_0005075 in glioma. QRT-PCR results demonstrated that SIRT1 was significantly down-regulated in glioma tissues and cell lines. High level of SIRT1 predicted better prognosis of glioma patients. Rescue experiments confirmed that SIRT1 was responsible for the regulatory role of circ_0005075 in the malignant progression of glioma.

CONCLUSIONS: Circ_0005075 is up-regulated in glioma tissues and correlated with distant metastasis and poor prognosis of glioma patients. Furthermore, it aggravates the malignant progression of glioma by down-regulating SIRT1.

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