MiR-320a functions as a suppressor for gliomas by targeting SND1 and ?-catenin, and predicts the prognosis of patients.

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 ?-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 ?-catenin. Cox regression showed that miR-320a and SND1 were independent predictors and ?-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 ?-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 ?-catenin. Our findings demonstrate the potential values of miR-320a, SND1 and ?-catenin as prognostic biomarkers and therapeutic candidates for malignant gliomas.

SUBMITTER: Li H 

PROVIDER: S-EPMC5386717 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature