PMID- 29328367
OWN - NLM
STAT- MEDLINE
DCOM- 20180831
LR  - 20211204
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 52
IP  - 3
DP  - 2018 Mar
TI  - Tumorigenic proteins upregulated in the MYCN-amplified IMR-32 human neuroblastoma 
      cells promote proliferation and migration.
PG  - 787-803
LID - 10.3892/ijo.2018.4236 [doi]
AB  - Childhood neuroblastoma is one of the most common types of extra-cranial cancer 
      affecting children with a clinical spectrum ranging from spontaneous regression 
      to malignant and fatal progression. In order to improve the clinical outcomes of 
      children with high-risk neuroblastoma, it is crucial to understand the 
      tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, 
      bHLH transcription factor (MYCN) amplification has been implicated in the 
      malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma. In 
      this study, we used a SILAC approach to compare the proteomic signatures of 
      MYCN-amplified IMR-32 and non-MYCN-amplified SK-N-SH human neuroblastoma cells. 
      Tumorigenic proteins, including fatty-acid binding protein 5 (FABP5), L1-cell 
      adhesion molecule (L1-CAM), baculoviral IAP repeat containing 5 
      [BIRC5 (survivin)] and high mobility group protein A1 (HMGA1) were found to be 
      significantly upregulated in the IMR-32 compared to the SK-N-SH cells and mapped 
      to highly tumorigenic pathways including, MYC, MYCN, microtubule associated 
      protein Tau (MAPT), E2F transcription factor 1 (E2F1), sterol regulatory element 
      binding transcription factor 1 or 2 (SREBF1/2), hypoxia-inducible 
      factor 1alpha (HIF-1alpha), Sp1 transcription factor (SP1) and amyloid precursor 
      protein (APP). The transcriptional knockdown (KD) of MYCN, HMGA1, FABP5 and 
      L1-CAM significantly abrogated the proliferation of the IMR-32 cells at 48 h post 
      transfection. The early apoptotic rates were significantly higher in the IMR-32 
      cells in which FABP5 and MYCN were knocked down, whereas cellular migration was 
      significantly abrogated with FABP5 and HMGA1 KD compared to the controls. Of 
      note, L1-CAM, HMGA1 and FABP5 KD concomitantly downregulated MYCN protein 
      expression and MYCN KD concomitantly downregulated L1-CAM, HMGA1 and FABP5 
      protein expression, while survivin protein expression was significantly 
      downregulated by MYCN, HMGA1 and FABP5 KD. In addition, combined L1-CAM and FABP5 
      KD led to the concomitant downregulation of HMGA1 protein expression. On the 
      whole, our data indicate that this inter-play between MYCN and the highly 
      tumorigenic proteins which are upregulated in the malignant IMR-32 cells may be 
      fueling their aggressive behavior, thereby signifying the importance of 
      combination, multi-modality targeted therapy to eradicate this deadly childhood 
      cancer.
FAU - Zaatiti, Hayat
AU  - Zaatiti H
AD  - Department of Biology, Faculty of Sciences, University of Balamand, El-Koura, 
      Lebanon.
FAU - Abdallah, Jad
AU  - Abdallah J
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese American 
      University, Byblos 1102-2801, Lebanon.
FAU - Nasr, Zeina
AU  - Nasr Z
AD  - Department of Biology, Faculty of Sciences, University of Balamand, El-Koura, 
      Lebanon.
FAU - Khazen, George
AU  - Khazen G
AD  - School of Arts and Sciences, Lebanese American University, Byblos 1102-2801, 
      Lebanon.
FAU - Sandler, Anthony
AU  - Sandler A
AD  - Sheikh Zayed Institute for Pediatric Surgical Innovation, Joseph E. Robert Jr. 
      Center for Surgical Care, Children's National Medical Center, Washington, DC 
      20010, USA.
FAU - Abou-Antoun, Tamara J
AU  - Abou-Antoun TJ
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese American 
      University, Byblos 1102-2801, Lebanon.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180104
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (MAS1 protein, human)
RN  - 0 (MYCN protein, human)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Carcinogenesis/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Child
MH  - Down-Regulation
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques/methods
MH  - Humans
MH  - N-Myc Proto-Oncogene Protein/genetics/*metabolism
MH  - Neuroblastoma/*genetics/pathology
MH  - Proteomics/methods
MH  - Proto-Oncogene Mas
MH  - RNA, Small Interfering/metabolism
MH  - *Transcriptional Activation
MH  - Up-Regulation
PMC - PMC5807036
COIS- Competing interests The authors declare that they have no competing interests.
EDAT- 2018/01/13 06:00
MHDA- 2018/09/01 06:00
PMCR- 2018/01/04
CRDT- 2018/01/13 06:00
PHST- 2017/09/20 00:00 [received]
PHST- 2017/12/05 00:00 [accepted]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/09/01 06:00 [medline]
PHST- 2018/01/13 06:00 [entrez]
PHST- 2018/01/04 00:00 [pmc-release]
AID - ijo-52-03-0787 [pii]
AID - 10.3892/ijo.2018.4236 [doi]
PST - ppublish
SO  - Int J Oncol. 2018 Mar;52(3):787-803. doi: 10.3892/ijo.2018.4236. Epub 2018 Jan 4.