miR-320a functions as a suppressor for gliomas by targeting SND1 and β-catenin, and predicts the prognosis of patients
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Huining Li1,2,3,*, Lin Yu4,*, Jing Liu1,2,3,*, Xiuwu Bian5, Cuijuan Shi1,2,3, Cuiyun Sun1,2,3, Xuexia Zhou1,2,3, Yanjun Wen1,2,3, Dan Hua1,2,3, Shujun Zhao1,2,6, Linlin Ren1,2,3, Tongling An1,2,3, Wenjun Luo1,2,3, Qian Wang1,2,3, Shizhu Yu1,2,3
1Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
2Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin, China
3Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
4Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Tianjin Medical University, Tianjin, China
5Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
6Laboratory of Hormone and Development, Ministry of Health, Institute of Endocrinology, Tianjin Medical University, Tianjin, China
*These authors have contributed equally to this work
Shizhu Yu, email: [email protected]
Qian Wang, email: [email protected]
Keywords: gliomas, miR-320a, SND1, β-catenin, prognosis
Received: April 04, 2016 Accepted: January 03, 2017 Published: February 01, 2017
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.
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