PMID- 30914203
OWN - NLM
STAT- MEDLINE
DCOM- 20200406
LR  - 20200408
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 512
IP  - 3
DP  - 2019 May 7
TI  - The short interference RNA (siRNA) targeting NMUR2 relieves nociception in a bone 
      cancer pain model of rat through PKC-ERK and PI3K-AKT pathways.
PG  - 616-622
LID - S0006-291X(19)30450-4 [pii]
LID - 10.1016/j.bbrc.2019.03.067 [doi]
AB  - BACKGROUND/AIM: Bone cancer pain (BCP) causes troubles and burdens to patients 
      globally. Increasing evidence proved that neuromedin U receptor 2 (NMUR2) was 
      involved in pains. Our study was performed to investigate the role of NMUR2 on 
      BCP and the underlying mechanism. METHODS: The rats were raised and BCP rat model 
      was established by injection with Walker 256 cells. The RNA and protein 
      expression levels of NMUR2 in rat neurons-dorsal spinal cord cells, RNdsc cells 
      were detected by qRT-PCR and western blot. The administration with NMUR2 was via 
      intrathecal injection with siRNA to silence NMUR2. The tolerance of rat to pain 
      was measured by mechanical allodynia test and presented by paw withdrawal 
      threshold (PWT) value. The effects on protein kinase C (PKC)/extracellular 
      regulated protein kinases (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein 
      kinase B (AKT) signal pathways were examined by western blot. RESULTS: The 
      expression of NMUR2 in both mRNA and protein levels was upregulated in BCP rat 
      model. In addition, siRNA injection significantly decreased the expression of 
      NMUR2 on the 3rd, 7th and 14th day. BCP group revealed lower PWT value compared 
      with control while NMUR2 silence increased the PWT value compared with negative 
      control. The phosphorylation of PKC, ERK, PI3K and AKT was increased in BCP model 
      while was decreased by si-NMUR2. PKC/ERK and PI3K/AKT inhibitor administration 
      increased the PWT value compared with BCP group. CONCLUSION: si-NMUR2 alleviates 
      BCP via inactivation of PKC/ERK and PI3K/AKT signal pathways.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Peng, Sheng
AU  - Peng S
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
FAU - Lu, Yingjun
AU  - Lu Y
AD  - Department of Anesthesiology, Shanghai Songjiang District Central Hospital, 
      No.748 Zhongshan Middle Road, Shanghai, 201600, China. Electronic address: 
      luyingjun0023@sina.com.
FAU - Li, Pengyi
AU  - Li P
AD  - Department of Anesthesiology, Jiangsu Cancer Hospital, Jiangsu Institute of 
      Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, 
      No.42 Baiziting, Nanjing, 210009, China.
FAU - Liu, Peirong
AU  - Liu P
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
FAU - Shi, Xiaowei
AU  - Shi X
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
FAU - Liu, Chunliang
AU  - Liu C
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
FAU - Liu, Shasha
AU  - Liu S
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Anesthesiology, Seventh People's Hospital of Shanghai University of 
      TCM, No.358 Datong Road, Shanghai, 200137, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190323
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 0 (neuromedin U receptor)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/*complications
MH  - Cancer Pain/genetics/*therapy
MH  - Disease Models, Animal
MH  - MAP Kinase Signaling System
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Protein Kinase C/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/genetics/*therapeutic use
MH  - *RNAi Therapeutics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Neurotransmitter/*genetics/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Bone cancer pain
OT  - Interfering RNA
OT  - Neuromedin U receptor 2
OT  - PI3K/AKT
OT  - PKC/ERK
EDAT- 2019/03/28 06:00
MHDA- 2020/04/09 06:00
CRDT- 2019/03/28 06:00
PHST- 2019/03/06 00:00 [received]
PHST- 2019/03/12 00:00 [accepted]
PHST- 2019/03/28 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/03/28 06:00 [entrez]
AID - S0006-291X(19)30450-4 [pii]
AID - 10.1016/j.bbrc.2019.03.067 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 May 7;512(3):616-622. doi: 
      10.1016/j.bbrc.2019.03.067. Epub 2019 Mar 23.