Rui Zhang1, Hui Luo1, Shuai Wang1, Wanghao Chen1, Zhengxin Chen1, Hong-Wei Wang1, Yuanyuan Chen1, Jingmin Yang1, Xiaotian Zhang1, Wenting Wu1, Shu-Yu Zhang1, Shuying Shen1, Qingsheng Dong1, Yaxuan Zhang1, Tao Jiang1, Daru Lu1, Shiguang Zhao1, Yongping You1, Ning Liu1, Huibo Wang1. 1. Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China (R.Z., H.L., W.C., Z.C., Q.D., Y.Z., Y.Y., N.L., H.W.); Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China (S.W.); Department of Neurosurgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China (H-W.W.); State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes for Biomedical Sciences, Fudan University, Shanghai, China (Y.C., J.Y., D.L.); Department of Molecular Human Genetics, Baylor College of Medicine, Houston, Texas (X.Z.); Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry, University of California San Diego, La Jolla, California (W.W.); School of Radiation Medicine and Protection, Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China (S-Y.Z.); Institute of Biochemistry, Zhejiang University, Hangzhou, China (S.S.); Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China (S.Z.); Chinese Glioma Cooperative Group (T.J., Y.Y., N.L., H.W.).
Abstract
BACKGROUND: Increasing evidence has indicated that microRNAs (miRNAs) are strongly implicated in the initiation and progression of glioblastoma multiforme (GBM). Here, we identified a novel tumor suppressive miRNA, miR-377, and investigated its role and therapeutic effect for GBM. METHODS: MiRNA global screening was performed on GBM patient samples and adjacent nontumor brain tissues. The expression of miR-377 was detected by real-time reverse-transcription PCR. The effects of miR-377 on GBM cell proliferation, cell cycle progression, invasion, and orthotopic tumorigenicity were investigated The therapeutic effect of miR-377 mimic was explored in a subcutaneous GBM model. Western blot and luciferase reporter assay were used to identify the direct and functional target of miR-377. RESULTS: MiR-377 was markedly downregulated in human GBM tissues and cell lines. Overexpression of miR-377 dramatically inhibited cell growth both in culture and in orthotopic xenograft tumor models, blocked G1/S transition, and suppressed cell invasion in GBM cells. Importantly, introduction of miR-377 could strongly inhibit tumor growth in a subcutaneous GBM model. Subsequent investigation revealed that specificity protein 1 (Sp1) was a direct and functional target of miR-377 in GBM cells. Silencing of Sp1 recapitulated the antiproliferative and anti-invasive effects of miR-377, whereas restoring the Sp1 expression antagonized the tumor-suppressive function of miR-377. Finally, analysis of miR-377 and Sp1 levels in human GBM tissues revealed that miR-377 is inversely correlated with Sp1 expression. CONCLUSION: These findings reveal that miR-377/Sp1 signaling that may be required for GBM development and may consequently serve as a therapeutic target for the treatment of GBM.
BACKGROUND: Increasing evidence has indicated that microRNAs (miRNAs) are strongly implicated in the initiation and progression of glioblastoma multiforme (GBM). Here, we identified a novel tumor suppressive miRNA, miR-377, and investigated its role and therapeutic effect for GBM. METHODS: MiRNA global screening was performed on GBM patient samples and adjacent nontumor brain tissues. The expression of miR-377 was detected by real-time reverse-transcription PCR. The effects of miR-377 on GBM cell proliferation, cell cycle progression, invasion, and orthotopic tumorigenicity were investigated The therapeutic effect of miR-377 mimic was explored in a subcutaneous GBM model. Western blot and luciferase reporter assay were used to identify the direct and functional target of miR-377. RESULTS:MiR-377 was markedly downregulated in human GBM tissues and cell lines. Overexpression of miR-377 dramatically inhibited cell growth both in culture and in orthotopic xenograft tumor models, blocked G1/S transition, and suppressed cell invasion in GBM cells. Importantly, introduction of miR-377 could strongly inhibit tumor growth in a subcutaneous GBM model. Subsequent investigation revealed that specificity protein 1 (Sp1) was a direct and functional target of miR-377 in GBM cells. Silencing of Sp1 recapitulated the antiproliferative and anti-invasive effects of miR-377, whereas restoring the Sp1 expression antagonized the tumor-suppressive function of miR-377. Finally, analysis of miR-377 and Sp1 levels in human GBM tissues revealed that miR-377 is inversely correlated with Sp1 expression. CONCLUSION: These findings reveal that miR-377/Sp1 signaling that may be required for GBM development and may consequently serve as a therapeutic target for the treatment of GBM.
Authors: A Zannetti; S Del Vecchio; M V Carriero; R Fonti; P Franco; G Botti; G D'Aiuto; M P Stoppelli; M Salvatore Journal: Cancer Res Date: 2000-03-15 Impact factor: 12.701
Authors: A Formosa; E K Markert; A M Lena; D Italiano; E Finazzi-Agro'; A J Levine; S Bernardini; A V Garabadgiu; G Melino; E Candi Journal: Oncogene Date: 2013-10-28 Impact factor: 9.867
Authors: Darukeshwara Joladarashi; Venkata Naga Srikanth Garikipati; Rajarajan A Thandavarayan; Suresh K Verma; Alexander R Mackie; Mohsin Khan; Anna M Gumpert; Arvind Bhimaraj; Keith A Youker; Cesar Uribe; Sahana Suresh Babu; Prince Jeyabal; Raj Kishore; Prasanna Krishnamurthy Journal: J Am Coll Cardiol Date: 2015-11-17 Impact factor: 24.094