Abstract
miR-320a downexpression contributes to tumorigenesis in several human cancers. However, the relevance of miR-320a to prognosis, proliferation and invasion in gliomas remains unclear. In this study, we demonstrated that miR-320a expression was decreased in human glioma tissues and cell lines. Moreover, miR-320a expression was inversely correlated with glioma grades and Ki-67 index, but positively correlated with patients’ survival. Contrarily, SND1 and β-catenin expressions were positively correlated with glioma grades and Ki-67 index, but inversely correlated with miR-320a expression and patients’ survival. Furthermore, two subgroups with distinct prognoses in our glioma patients of different grade, IDH status, age and KPS were identified according to expression of miR-320a, SND1 or β-catenin. Cox regression showed that miR-320a and SND1 were independent predictors and β-catenin was an auxiliary predictor for patients’ survival. miR-320a overexpression suppressed the G1/S phase transition, proliferation, migration and invasion of glioblastoma cells. Mechanistically, we validated SND1 and β-catenin as direct targets of miR-320a, and found that miR-320a overexpression increased SND1-inhibited tumor suppressor p21WAF1 and decreased Smad2, Smad4, MMP2, MMP7 and cyclinD1, the pivotal downstream effectors of SND1 or β-catenin. Our findings demonstrate the potential values of miR-320a, SND1 and β-catenin as prognostic biomarkers and therapeutic candidates for malignant gliomas.
Highlights
Gliomas are the most frequent primary brain tumors [1, 2]
We demonstrated that miR-320a expression in gliomas was lower than that in the control (P
We found that glioma patients in the same grade, IDH status, age and Karnofsky performance score (KPS) groups could be divided into two subgroups with different outcomes based on miR320a expression, i.e., the higher expression of miR-320a was, the better prognosis of patients
Summary
Gliomas are the most frequent primary brain tumors [1, 2]. High-grade gliomas, such as glioblastoma multiform (GBM), are characterized by rapid growth and relentless invasion, which makes radical resection almost impossible for them [3]. Human miR-320 family has 5 mature members termed as miR-320a to e. They are encoded by the loci on chromosome 1, 8, 13, 19 and X, respectively. The aberrant expression of miR-320a has been reported in various malignant tumors [5,6,7]. In bladder and colon cancers, www.impactjournals.com/oncotarget its expression level is extremely low [8,9], whereas in retinoblastoma, higher miR-320a level is associated with a more malignant phenotype [10], suggesting that function of this miRNA may be distinct and even opposite in different tumors. The expression pattern, prognostic significance and biologic functions of miR320a remain to be fully elucidated in gliomas
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