PMID- 23834154
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20230815
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 14
IP  - 10
DP  - 2013 Sep
TI  - Targeting miR-21 induces autophagy and chemosensitivity of leukemia cells.
PG  - 1135-43
AB  - Overexpression of oncomiR-21 has been observed in most cancer types, such as 
      leukemia. This miR has been implicated in a number of cellular processes, 
      including chemoresistance, possibly by directly modulating the expression of 
      several apoptotic related proteins. It was recently shown to directly target 
      Bcl-2 mRNA and upregulate Bcl-2 protein expression. Nevertheless, the possible 
      effect of miR-21 in autophagy has never been addressed. This study investigates 
      the effects of targeting miR-21 with antimiRs on chronic myeloid leukemia 
      cellular autophagy and on associated drug sensitivity. We observed that miR-21 
      downregulation decreased cellular viability and proliferation, although no 
      changes to the normal cell cycle profile were observed. miR-21 downregulation 
      also caused increased programmed cell death and a decrease in the expression 
      levels of Bcl-2 protein, although PARP cleavage was not affected, indicating that 
      apoptosis was not the relevant mechanism underlying the observed results. 
      Treatment with antimiR-21 caused an increase in the autophagy related proteins 
      Beclin-1, Vps34 and LC3-II. Accordingly, autophagic vacuoles were visualized both 
      by monodansylcadaverine (MDC) and acridine orange (AO) staining and also by 
      transmission electron microscopy (TEM). Additionally, miR-21 downregulation 
      increased K562 and KYO-1 cellular sensitivity to etoposide or doxorubicin. This 
      chemosensitivity was reverted by pre-treating cells with 3-MA, an autophagy 
      inhibitor. Finally, serum starvation (an autophagy inducer) also increased 
      sensitivity to these drugs, confirming that autophagy sensitized these cells to 
      the effect of these drugs. To the best of our knowledge, this is the first 
      description of autophagy induction via miR-21 targeting and its involvement in 
      drug sensitivity.
FAU - Seca, Hugo
AU  - Seca H
AD  - Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and 
      Immunology of the University of Porto, Porto, Portugal.
FAU - Lima, Raquel T
AU  - Lima RT
FAU - Lopes-Rodrigues, Vanessa
AU  - Lopes-Rodrigues V
FAU - Guimaraes, Jose E
AU  - Guimaraes JE
FAU - Almeida, G M
AU  - Almeida GM
FAU - Vasconcelos, M Helena
AU  - Vasconcelos MH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Apoptosis/drug effects/genetics
MH  - Apoptosis Regulatory Proteins/genetics/metabolism
MH  - Autophagy/*drug effects/*genetics
MH  - Cell Cycle/drug effects/*genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects/*genetics
MH  - Doxorubicin/metabolism/therapeutic use
MH  - Etoposide/metabolism/therapeutic use
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, bcl-2
MH  - Humans
MH  - K562 Cells
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/*genetics/pathology
MH  - MicroRNAs/*genetics/metabolism
EDAT- 2013/07/10 06:00
MHDA- 2014/02/14 06:00
CRDT- 2013/07/10 06:00
PHST- 2013/06/28 00:00 [received]
PHST- 2013/07/01 00:00 [accepted]
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
AID - CDT-EPUB-01-53707 [pii]
AID - 10.2174/13894501113149990185 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2013 Sep;14(10):1135-43. doi: 10.2174/13894501113149990185.