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. 2019 Jul;18(1):359-367.
doi: 10.3892/ol.2019.10335. Epub 2019 May 7.

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA-218

Xuezhi Tong  1 , Pei Yang  1 , Kuanyu Wang  2 , Yanwei Liu  1 , Xiu Liu  2 , Xia Shan  2 , Ruoyu Huang  2 , Ke'Nan Zhang  2 , Jiangfei Wang  1
Affiliations

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA-218

Xuezhi Tong et al. Oncol Lett. 2019 Jul.

Abstract

Accumulating evidence has revealed that survivin expression is associated with a malignant phenotype and poor prognosis in glioma. Survivin is also a potential target of microRNA (miRNA/miR)-218. The aim of the present study was to investigate the expression and function of survivin in glioblastoma, and to examine the association between survivin and miR-218. For that purpose, survivin mRNA levels were analyzed in 144 frozen samples of glioblastoma using whole-genome RNA sequencing. In vitro cell proliferation, migration, invasion and apoptosis assays were performed, and survivin expression was detected by western blotting. The results revealed that the mRNA expression levels of survivin were negatively and significantly associated with overall survival in glioblastoma. Further in vitro analyses suggested that miR-218 may inhibit the expression of survivin. Expression of miR-218 in the LN229 cell line was significantly lower than that in the immortalized human gliocyte HEB cell line. miR-218 markedly inhibited tumor cell proliferation, migration and invasion capacities, and decreased apoptosis. miR-218 also inhibited the expression of survivin. These results indicated that survivin may be a target of miR-218 and could serve as a predictive biomarker.

Keywords: glioblastoma; miRNA-218; prognosis; proliferation; survivin.

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Figures

Figure 1.
Figure 1.
Kaplan-Meier survival curves showing OS. (A) OS according to the expression of survivin; (B and C) OS of patients treated with RT + TMZ or RT only in the (B) high and (C) low-survivin expression groups. OS, overall survival; RT, radiotherapy; TMZ, temozolomide.
Figure 2.
Figure 2.
Expression of survivin in clinical tissue samples. (A and B) Protein expression of survivin in glioma and adjacent tissues. (C) Immunohistochemistry showing the expression of survivin in gliomas and adjacent tissues. ***P<0.001.
Figure 3.
Figure 3.
Function of miR-218 in glioblastoma. miR-218 expression in (A) cell lines and (B) clinical samples, as detected by RT-qPCR and (C) fluorescence in situ hybridization. (D) Expression of miR-218 in LN229 cells transfected with miR-218 mimics or NC. (E-H) Proliferation, migration, invasion and apoptosis of LN229 cells transfected with miR-218 mimics or NC. *P<0.05, **P<0.01 and ***P<0.001. miR, microRNA; NC, negative control; 7-AAD, 7-amino-actinomycin D; APC, allophycocyanin.
Figure 4.
Figure 4.
Survivin is a target of miR-218. Upon transfection with miR-218 mimics, (A) survivin mRNA was assessed by RT-qPCR and (B and C) survivin protein was determined by western blot analysis in LN229 cells. *P<0.05 and ***P<0.001. miR, microRNA; NC, negative control.
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