MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Naveenkumar Perumal, Ranjana K. Kanchan, David Doss, Noah Bastola, Pranita Atri, Ramakanth Chirravuri-Venkata, Ishwor Thapa, Raghupathy Vengoji, Shailendra K. Maurya, David Klinkebiel, Geoffrey A. Talmon, Mohd W. Nasser, Surinder K. Batra, Sidharth Mahapatra

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number195
JournalActa neuropathologica communications
Volume9
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • 17p13.3
  • Group 3 medulloblastoma
  • Nuclear factor I/B
  • c-Myc
  • miR-212-3p

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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