PMID- 25266796
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20220330
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 36
IP  - 1
DP  - 2015 Jan
TI  - A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer 
      T24 cells via the PTEN/PI3K/AKT/mTOR axis.
PG  - 383-91
LID - 10.1007/s13277-014-2617-2 [doi]
AB  - Cancer cells exhibit the ability to metabolise glucose to lactate even under 
      aerobic conditions for energy. This phenomenon is known as the Warburg effect and 
      can be a potential target to kill cancer cells. Several studies have shown 
      evidence for interplay between microRNAs and key metabolic enzyme effecters, 
      which can facilitate the Warburg effect in cancer cells. In the present study, a 
      microRNA sponge forcibly expressed using a lentiviral vector was utilised to 
      knock down miR-21 expression in vitro. qPCR and Western blot assays were 
      performed to evaluate the expression of a regulatory factor related to aerobic 
      glycolysis and the signalling pathway it regulates. In bladder cancer specimens, 
      expression levels of glycolysis-related genes [glucose transporter (GLUT)1, 
      GLUT3, lactic dehydrogenase (LDH)A, LDHB, hexokinase (HK)1, HK2, pyruvate kinase 
      type M (PKM) and hypoxia-inducible factor 1-alpha (HIF-1alpha)] were higher in tumour 
      tissues than in adjacent tissues, suggesting the role of glycolysis in bladder 
      cancer. miR-21 inhibition in bladder cancer cell lines resulted in reduction in 
      tumour aerobic glycolysis. Decrease in glucose uptake and lactate production was 
      observed upon expression of the miR-21 sponge, which promoted phosphatase and 
      tensin homologue (PTEN) expression, decreased phosphorylated AKT and deactivated 
      mTOR. Furthermore, messenger RNA (mRNA) and protein expression levels of 
      glycolysis-related genes were also lower in miR-21 sponge cells compared to 
      miR-21 control cells. Our findings suggest that miR-21 acts as a molecular switch 
      to regulate aerobic glycolysis in bladder cancer cells via the 
      PTEN/phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Blocking miR-21 
      function can be an effective diagnostic and therapeutic approach either by itself 
      or in combination with existing methods to treat bladder cancer.
FAU - Yang, Xiao
AU  - Yang X
AD  - Department of Urology, The First Affiliated Hospital, Nanjing Medical University, 
      Nanjing, China.
FAU - Cheng, Yidong
AU  - Cheng Y
FAU - Li, Pengchao
AU  - Li P
FAU - Tao, Jun
AU  - Tao J
FAU - Deng, Xiaheng
AU  - Deng X
FAU - Zhang, Xiaolei
AU  - Zhang X
FAU - Gu, Min
AU  - Gu M
FAU - Lu, Qiang
AU  - Lu Q
FAU - Yin, Changjun
AU  - Yin C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140930
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Line, Tumor
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Glucose/metabolism
MH  - *Glycolysis
MH  - Humans
MH  - Lentivirus
MH  - MicroRNAs/*genetics/metabolism
MH  - PTEN Phosphohydrolase/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transduction, Genetic
MH  - Urinary Bladder Neoplasms
EDAT- 2014/10/01 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/10/01 06:00
PHST- 2014/08/07 00:00 [received]
PHST- 2014/09/09 00:00 [accepted]
PHST- 2014/10/01 06:00 [entrez]
PHST- 2014/10/01 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - 10.1007/s13277-014-2617-2 [doi]
PST - ppublish
SO  - Tumour Biol. 2015 Jan;36(1):383-91. doi: 10.1007/s13277-014-2617-2. Epub 2014 Sep 
      30.