TY - JOUR
T1 - MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)
AU - Perumal, Naveenkumar
AU - Kanchan, Ranjana K.
AU - Doss, David
AU - Bastola, Noah
AU - Atri, Pranita
AU - Chirravuri-Venkata, Ramakanth
AU - Thapa, Ishwor
AU - Vengoji, Raghupathy
AU - Maurya, Shailendra K.
AU - Klinkebiel, David
AU - Talmon, Geoffrey A.
AU - Nasser, Mohd W.
AU - Batra, Surinder K.
AU - Mahapatra, Sidharth
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - 17p13.3
KW - Group 3 medulloblastoma
KW - Nuclear factor I/B
KW - c-Myc
KW - miR-212-3p
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UR - http://www.scopus.com/inward/citedby.url?scp=85121449387&partnerID=8YFLogxK
U2 - 10.1186/s40478-021-01299-z
DO - 10.1186/s40478-021-01299-z
M3 - Article
C2 - 34922631
AN - SCOPUS:85121449387
SN - 2051-5960
VL - 9
JO - Acta neuropathologica communications
JF - Acta neuropathologica communications
IS - 1
M1 - 195
ER -