PMID- 30252847
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20231103
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 9
DP  - 2018
TI  - Human cellular mitochondrial remodelling is governed by miR-2909 RNomics.
PG  - e0203614
LID - 10.1371/journal.pone.0203614 [doi]
LID - e0203614
AB  - BACKGROUND: There exists a general recognition of the fact that mitochondrial 
      remodelling as a result of aerobic glycolysis ensures human somatic cells to 
      revert to a more primitive-form exhibiting stem-like phenotype. The present study 
      is an attempt to demonstrate that miR-2909 RNomics within human peripheral blood 
      mononuclear cells (PBMCs) has the inherent capacity to re-program these cells to 
      exhibit mitochondrial remodelling paralleled by aerobic glycolysis together with 
      intracellular lipid inclusions. Such re-programmed PBMCs also expressed genes 
      having ability to sustain their de-differentiation state and survival. MATERIAL 
      AND METHODS: Human PBMCs were programed to ectopically express miR-2909. 
      Expression levels of genes including glucose transporter-1 (Glut-1), hexokinase 
      (HK), hypoxia inducia factor-1 (HIF-1alpha), c-Myc, p53,mechanistic target of 
      rapamycin complex (mTORC1), polycombcomplex protein (Bmi-1), Notch,Nanog,Tie-2, 
      Oct-4,CD59, p53, CD34, B-cell lymphoma-2 (Bcl2),sterol regulatory element-binding 
      protein2 (SREBP2), peroxisome proliferator-activated receptor gamma (PPARgamma) 
      nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), 
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1alpha) 
      within miR-2909 expression vector transfected human PBMCs as well as PBMCs 
      transfected with control vector containing scrambled sequence after 48h 
      post-transfection using RT-qPCR and cellular ultrastructural features induced by 
      miR-2909 ectopic expression were observed using transmission electron microscopy 
      and morphometric analysis of an electron micrograph. RESULTS: Ectopic expression 
      of miR-2909 within human PBMCs resulted in their reprogramming into stem-like 
      phenotype indicated by mitochondrial globular shaped coupled with cristae-poor 
      morphology. Nuclear to cytoplasmic ratio (N/C), quantification of ATP levels, 
      GSSG/GSH ratio, mitochondrial cytochrome c oxidase activity, secreted lactate 
      concentrations, activity of antioxidant enzymes, levels of esterified cholesterol 
      and triglycerides and flow-cytometric detection of apoptosis confirmed the 
      compromised nature of mitochondrial function induced by ectopic miR-2909 
      expression in human PBMCs. CONCLUSION: Based upon these results we propose that 
      AATF gene-encoded miR-2909 may act as an epigenetic switch for cellular 
      aerobic-glycolysis to ensure de-differentiation.
FAU - Malik, Deepti
AU  - Malik D
AD  - Molecular Biology Unit, Experimental Medicine and Biotechnology, Postgraduate 
      Institute of Medical Education and Research, Chandigarh (India).
FAU - Kaul, Deepak
AU  - Kaul D
AUID- ORCID: 0000-0002-6869-5094
AD  - Molecular Biology Unit, Experimental Medicine and Biotechnology, Postgraduate 
      Institute of Medical Education and Research, Chandigarh (India).
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180925
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD59 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MIRN2909 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (PPAR gamma)
RN  - 0 (SREBF2 protein, human)
RN  - 0 (Sterol Regulatory Element Binding Protein 2)
RN  - 0 (TFAM protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Receptor, TIE-2)
RN  - EC 2.7.10.1 (TEK protein, human)
SB  - IM
MH  - Adult
MH  - CD59 Antigens/metabolism
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Female
MH  - Humans
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Male
MH  - MicroRNAs/*genetics/*metabolism
MH  - Mitochondria/*metabolism
MH  - Mitochondrial Proteins/metabolism
MH  - Octamer Transcription Factor-3/metabolism
MH  - PPAR gamma/metabolism
MH  - Receptor, TIE-2/metabolism
MH  - Sterol Regulatory Element Binding Protein 2/metabolism
MH  - Transcription Factors/metabolism
PMC - PMC6155498
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/09/27 06:00
MHDA- 2019/02/26 06:00
PMCR- 2018/09/25
CRDT- 2018/09/26 06:00
PHST- 2018/02/27 00:00 [received]
PHST- 2018/08/23 00:00 [accepted]
PHST- 2018/09/26 06:00 [entrez]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2018/09/25 00:00 [pmc-release]
AID - PONE-D-18-05789 [pii]
AID - 10.1371/journal.pone.0203614 [doi]
PST - epublish
SO  - PLoS One. 2018 Sep 25;13(9):e0203614. doi: 10.1371/journal.pone.0203614. 
      eCollection 2018.