miR-320a functions as a suppressor for gliomas by targeting SND1 and β-catenin, and predicts the prognosis of patients

Abstract

// Huining Li 1, 2, 3, * , Lin Yu 4, * , Jing Liu 1, 2, 3, * , Xiuwu Bian 5 , Cuijuan Shi 1, 2, 3 , Cuiyun Sun 1, 2, 3 , Xuexia Zhou 1, 2, 3 , Yanjun Wen 1, 2, 3 , Dan Hua 1, 2, 3 , Shujun Zhao 1, 2, 6 , Linlin Ren 1, 2, 3 , Tongling An 1, 2, 3 , Wenjun Luo 1, 2, 3 , Qian Wang 1, 2, 3 , Shizhu Yu 1, 2, 3 1 Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 2 Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin, China 3 Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China 4 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Tianjin Medical University, Tianjin, China 5 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China 6 Laboratory of Hormone and Development, Ministry of Health, Institute of Endocrinology, Tianjin Medical University, Tianjin, China * These authors have contributed equally to this work Correspondence to: Shizhu Yu, email: tjyushizhu@yahoo.com Qian Wang, email: wangqiantni@163.com Keywords: gliomas, miR-320a, SND1, β-catenin, prognosis Received: April 04, 2016      Accepted: January 03, 2017      Published: February 01, 2017 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 p21 WAF1 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.