PMID- 27350898
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160628
LR  - 20220330
IS  - 2167-8359 (Print)
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 4
DP  - 2016
TI  - Integrated microRNA, gene expression and transcription factors signature in 
      papillary thyroid cancer with lymph node metastasis.
PG  - e2119
LID - 10.7717/peerj.2119 [doi]
LID - e2119
AB  - Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy 
      originating from the follicle cells in the thyroid. Despite a good overall 
      prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) 
      have progressive disease and poorer prognosis. MicroRNAs are a class of 
      non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene 
      expression and these molecules have been shown to play a role in LNM. The 
      integrated analysis of miRNAs and gene expression profiles together with 
      transcription factors (TFs) has been shown to improve the identification of 
      functional miRNA-target gene-TF relationships, providing a more complete view of 
      molecular events underlying metastasis process. Objectives. We reanalyzed The 
      Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed 
      miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative 
      (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that 
      regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a 
      significantly shorter disease-free survival rate compared to PTC patients without 
      LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 
      significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 
      were upregulated and 71 were downregulated. The five topmost deregulated miRNAs 
      were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In 
      addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal 
      thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal 
      thyroid. We found four significant enrichment pathways potentially involved in 
      metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell 
      adhesion molecules (CAMs), leukocyte transendothelial migration and 
      cytokine-cytokine receptor interaction. OxPhos was the most significantly 
      perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related 
      genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB 
      transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. 
      Conclusion. We found evidence of five miRNAs differentially expressed in PTC 
      LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to 
      the lymph node in PTC. We postulate that hsa-miR-301b might be involved in 
      regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of 
      our knowledge, the roles of these TFs have been studied in PTC but the precise 
      role of this miRNA with these TFs in LNM in PTC has not been investigated.
FAU - Ab Mutalib, Nurul-Syakima
AU  - Ab Mutalib NS
AD  - UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, 
      Kuala Lumpur, Malaysia.
FAU - Othman, Sri Noraima
AU  - Othman SN
AD  - UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, 
      Kuala Lumpur, Malaysia.
FAU - Mohamad Yusof, Azliana
AU  - Mohamad Yusof A
AD  - UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, 
      Kuala Lumpur, Malaysia.
FAU - Abdullah Suhaimi, Shahrun Niza
AU  - Abdullah Suhaimi SN
AD  - Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, 
      Cheras, Kuala Lumpur, Malaysia.
FAU - Muhammad, Rohaizak
AU  - Muhammad R
AD  - Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, 
      Cheras, Kuala Lumpur, Malaysia.
FAU - Jamal, Rahman
AU  - Jamal R
AD  - UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, 
      Kuala Lumpur, Malaysia.
LA  - eng
PT  - Journal Article
DEP - 20160615
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
PMC - PMC4918724
OTO - NOTNLM
OT  - Gene expression
OT  - Lymph node
OT  - MicroRNA
OT  - Papillary thyroid carcinoma
COIS- The authors declare that there are no competing interests.
EDAT- 2016/06/29 06:00
MHDA- 2016/06/29 06:01
PMCR- 2016/06/15
CRDT- 2016/06/29 06:00
PHST- 2015/11/25 00:00 [received]
PHST- 2016/05/18 00:00 [accepted]
PHST- 2016/06/29 06:00 [entrez]
PHST- 2016/06/29 06:00 [pubmed]
PHST- 2016/06/29 06:01 [medline]
PHST- 2016/06/15 00:00 [pmc-release]
AID - 2119 [pii]
AID - 10.7717/peerj.2119 [doi]
PST - epublish
SO  - PeerJ. 2016 Jun 15;4:e2119. doi: 10.7717/peerj.2119. eCollection 2016.