PMID- 27388765
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20210719
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 7
DP  - 2016
TI  - miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for 
      Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and 
      Glioblastoma SNB19 Cells.
PG  - e0158537
LID - 10.1371/journal.pone.0158537 [doi]
LID - e0158537
AB  - Glioblastoma is the most common and malignant brain tumor in humans. It is a 
      heterogeneous tumor harboring glioblastoma stem cells (GSC) and other 
      glioblastoma cells that survive and sustain tumor growth in a hypoxic environment 
      via induction of autophagy and resistance to apoptosis. So, a therapeutic 
      strategy to inhibit autophagy and promote apoptosis could greatly help control 
      growth of glioblastoma. We created hypoxia using sodium sulfite (SS) for 
      induction of substantiated autophagy in human GSC and glioblastoma SNB19 cells. 
      Induction of autophagy was confirmed by acridine orange (AO) staining and 
      significant increase in Beclin-1 in autophagic cells. microRNA database (miRDB) 
      search suggested that miR-30e could suppress the autophagy marker Beclin-1 and 
      also inhibit the caspase activation inhibitors (AVEN and BIRC6). Pro-apoptotic 
      effect of proanthocyanidin (PAC) has not yet been explored in glioblastoma cells. 
      Combination of 50 nM miR-30e and 150 muM PAC acted synergistically for inhibition 
      of viability in both cells. This combination therapy most effectively altered 
      expression of molecules for inhibition of autophagy and induced extrinsic and 
      intrinsic pathways of apoptosis through suppression of AVEN and BIRC6. 
      Collectively, combination of miR-30e and PAC is a promising therapeutic strategy 
      to inhibit autophagy and increase apoptosis in GSC and SNB19 cells.
FAU - Chakrabarti, Mrinmay
AU  - Chakrabarti M
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina, United States of America.
FAU - Klionsky, Daniel J
AU  - Klionsky DJ
AD  - Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United 
      States of America.
FAU - Ray, Swapan K
AU  - Ray SK
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina, United States of America.
LA  - eng
GR  - R01 GM053396/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20160707
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (AVEN protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BIRC6 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (MIRN30b microRNA, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Proanthocyanidins)
RN  - 0 (Sulfites)
RN  - 18206-61-6 (proanthocyanidin)
RN  - F30N4O6XVV (Acridine Orange)
RN  - VTK01UQK3G (sodium sulfite)
SB  - IM
MH  - Acridine Orange/chemistry
MH  - Adaptor Proteins, Signal Transducing/*antagonists & inhibitors
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Apoptosis Regulatory Proteins/*antagonists & inhibitors
MH  - Autophagy/*drug effects
MH  - Beclin-1/chemistry
MH  - Brain Neoplasms/drug therapy/*pathology
MH  - Cell Line, Tumor
MH  - Gene Expression Profiling
MH  - Glioblastoma/drug therapy/*pathology
MH  - Humans
MH  - Hypoxia
MH  - Inhibitor of Apoptosis Proteins/*antagonists & inhibitors
MH  - Membrane Proteins/*antagonists & inhibitors
MH  - MicroRNAs/*genetics
MH  - Neoplastic Stem Cells/drug effects/metabolism
MH  - Proanthocyanidins/*pharmacology
MH  - Signal Transduction/drug effects
MH  - Sulfites
MH  - Transfection
PMC - PMC4936720
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/07/09 06:00
MHDA- 2017/08/02 06:00
PMCR- 2016/07/07
CRDT- 2016/07/09 06:00
PHST- 2015/09/23 00:00 [received]
PHST- 2016/06/17 00:00 [accepted]
PHST- 2016/07/09 06:00 [entrez]
PHST- 2016/07/09 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2016/07/07 00:00 [pmc-release]
AID - PONE-D-15-42175 [pii]
AID - 10.1371/journal.pone.0158537 [doi]
PST - epublish
SO  - PLoS One. 2016 Jul 7;11(7):e0158537. doi: 10.1371/journal.pone.0158537. 
      eCollection 2016.