PMID- 28994148
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20231213
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 50
IP  - 6
DP  - 2017 Dec
TI  - LincRNA-p21 suppresses development of human prostate cancer through inhibition of 
      PKM2.
LID - 10.1111/cpr.12395 [doi]
LID - e12395
AB  - OBJECTIVES: Previously, we found that long intergenic non-coding RNA-p21 
      (lincRNA-p21) inhibited the development of human prostate cancer. However, the 
      underlying molecular mechanisms are poorly understood. Here, we attempted to 
      investigate the downstream targets of lincRNA-p21 in prostate cancer. MATERIALS 
      AND METHODS: Expression of lincRNA-p21 and PKM2 was determined by qRT-PCR and 
      Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role 
      of PKM2 on the enhanced cell proliferation and glycolysis of lincRNA-p21-silenced 
      prostate cancer cells. A xenograft mouse model was performed to investigate the 
      effect of PKM2 suppression, glycolytic or mammalian target of rapamycin (mTOR) 
      inhibitor on the tumorigenic capacity of lincRNA-p21-silenced prostate cancer 
      cells. RESULTS: We revealed that lincRNA-p21 silencing in DU145 and LNCaP cells 
      induced up-regulation of PKM2 and activation of glycolysis, which could be 
      reversed by PKM2 knockdown or rapamycin treatment. We also found that the 
      proliferation and tumorigenesis of lincRNA-p21-silenced prostate cancer cells 
      were significantly inhibited after knocking down PKM2. 3-bromopyruvate (3-Brpa) 
      or rapamycin treatment largely decreased the tumour burden. Importantly, PKM2 
      expression was inversely correlated with the lincRNA-p21 level and the survival 
      of prostate cancer patients. CONCLUSIONS: We demonstrated that lincRNA-p21 
      blunted the prostate cancer cell proliferation and tumorigenic capacity through 
      down-regulation of PKM2. Therefore, targeting PKM2 or glycolysis might be a 
      therapeutic strategy in prostate cancer patients with lowly expressed 
      lincRNA-p21.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Wang, Xiaohai
AU  - Wang X
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Xu, Yongzhi
AU  - Xu Y
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Wang, Xingjie
AU  - Wang X
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Jiang, Chenyi
AU  - Jiang C
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Han, Sha
AU  - Han S
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Dong, Kai
AU  - Dong K
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Shen, Mengjun
AU  - Shen M
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
FAU - Xu, Dongliang
AU  - Xu D
AUID- ORCID: 0000-0002-6739-613X
AD  - Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, 200080, China.
LA  - eng
PT  - Journal Article
DEP - 20171009
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Pyruvates)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Thyroid Hormones)
RN  - 63JMV04GRK (bromopyruvate)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Down-Regulation
MH  - Glycolysis/physiology
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Prostatic Neoplasms/*genetics
MH  - Pyruvates/pharmacology
MH  - RNA, Long Noncoding/*genetics
MH  - Thyroid Hormones/*metabolism
MH  - Thyroid Hormone-Binding Proteins
PMC - PMC6529145
COIS- None.
EDAT- 2017/10/11 06:00
MHDA- 2017/12/08 06:00
PMCR- 2017/10/09
CRDT- 2017/10/11 06:00
PHST- 2017/04/01 00:00 [received]
PHST- 2017/09/14 00:00 [accepted]
PHST- 2017/10/11 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
PHST- 2017/10/11 06:00 [entrez]
PHST- 2017/10/09 00:00 [pmc-release]
AID - CPR12395 [pii]
AID - 10.1111/cpr.12395 [doi]
PST - ppublish
SO  - Cell Prolif. 2017 Dec;50(6):e12395. doi: 10.1111/cpr.12395. Epub 2017 Oct 9.