期刊论文详细信息
Acta Neuropathologica Communications
MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)
Surinder K. Batra1  Ranjana K. Kanchan1  Raghupathy Vengoji1  Naveenkumar Perumal1  Pranita Atri1  Mohd W. Nasser1  Shailendra K. Maurya1  Ramakanth Chirravuri-Venkata1  David Klinkebiel1  Sidharth Mahapatra2  David Doss3  Noah Bastola4  Geoffrey A. Talmon5  Ishwor Thapa6 
[1] Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 68198, Omaha, NE, USA;Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 68198, Omaha, NE, USA;Department of Pediatrics, University of Nebraska Medical Center, 68198, Omaha, NE, USA;Department of Biomedical Sciences, Creighton University School of Medicine, 68124, Omaha, NE, USA;Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 63110, St. Louis, MO, USA;Department of Pathology and Microbiology, University of Nebraska Medical Center, 68198, Omaha, NE, USA;School of Interdisciplinary Informatics, University of Nebraska at Omaha, 68182, Omaha, NE, USA;
关键词: 17p13.3;    c-Myc;    Group 3 medulloblastoma;    miR-212-3p;    Nuclear factor I/B;   
DOI  :  10.1186/s40478-021-01299-z
来源: Springer
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【 摘 要 】

Haploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors. First, we learned that miR-212-3p undergoes epigenetic silencing by histone modifications in group 3 tumors. Restoring its expression reduced cancer cell proliferation, migration, colony formation, and wound healing in vitro and attenuated tumor burden and improved survival in vivo. MiR-212-3p also triggered c-Myc destabilization and degradation, leading to elevated apoptosis. We then isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors and associated with poor survival. NFIB silencing reduced cancer cell proliferation, migration, and invasion. Concurrently, reduced medullosphere formation and stem cell markers (Nanog, Oct4, Sox2, CD133) were noted. These results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and identify a novel oncogenic target implicated in metastasis and tumor recurrence.

【 授权许可】

CC BY   

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