MYCN oncoprotein targets and their therapeutic potential.
Intriguingly, MV4-11 cells do not express
Mycn (Figure 5).
Lesne et al., "Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a
MYCN independent mechanism," Oncotarget, vol.
Targeting
MYCN IRES in MYCN-amplified neuroblastoma with miR-375 inhibits tumor growth and sensitizes tumor cells to radiation.
Honna et al., "Successful tandem (autologous-cord blood) SCT in advanced neuroblastomas with highly amplified
MYCN," Bone Marrow Transplantation, vol.
Cell line Site Stage Patient age Phase of therapy CHLA-15 Tumor 4 >1 DX CHLA-20 Tumor 4 1.5 PD-Ind CHLA-90 BM 4 8.5 PD-Auto-BMT LAN-5 BM Unknown 0.4 Unknown NUB-7 LN 4s/4 0.7 Unknown SH-SY5Y BM 4 4 PD-Ind BE(2)C BM 4 2.2 PD-Ind SK-N-BE(2) BM 4 2.2 PD-Ind Cell line
MYCN amp p53 mutant CHLA-15 N WT CHLA-20 N WT CHLA-90 N Mut LAN-5 A WT NUB-7 A WT SH-SY5Y N WT BE(2)C A Mut SK-N-BE(2) A Mut BM = bone marrow; B = bone; L = liver; P = pulmonary; LN = lymph node; DX = at diagnosis; PD-Ind = progressive disease on induction chemotherapy; BMT = bone marrow transplantation; PD-Auto-BMT = relapsed after myeloablative chemo-radiotherapy followed by bone marrow transplantation; WT = wild type; Mut = mutant; N = nonamplified; A = amplified.
Vider et al., "
MYCN and MYC regulate tumor proliferation and tumorigenesis directly through BMI1 in human neuroblastomas," The FASEB Journal, vol.
Induction of senescence in
MYCN amplified neuroblastoma cell lines by hydroxyurea.
The predicted targets of miR-145 were oncogenes myc myelocytomatosis viral-related oncogene (
MYCN), FOS, and yamaguchi sarcoma oncogene (YES); cell-cycle promoters such as cyclins D2 and L1; and mitogen-activated protein kinase (MAPK) transduction proteins such as MAP3K3 and MAP4K4 [40].
Moreover, the oncogene
MYCN, a member of the MYC family of basic helix-loop-helix transcription factors, has been described to bind the AURKA promoter either alone or in complex with the DNA methyl binding protein MeCP2 in the neuroblastoma derived cell line Kelly [14].
Clinically relevant pediatric factors that influence survival in children include stage, age, histology, tumor grade,
MYCN oncogene status, chromosome 11q status, and DNA ploidy.