PMID- 32377716
OWN - NLM
STAT- MEDLINE
DCOM- 20210305
LR  - 20210305
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 46
IP  - 1
DP  - 2020 Jul
TI  - HIKESHI silencing can enhance mild hyperthermia sensitivity in human oral 
      squamous cell carcinoma HSC‑3 cells.
PG  - 58-66
LID - 10.3892/ijmm.2020.4591 [doi]
AB  - Hyperthermia (HT) is considered to be of value as a treatment modality in various 
      cancers. However, the acquisition of thermotolerance in cancer cells due to the 
      induction of heat shock proteins (HSPs) makes HT less effective. Recent findings 
      have indicated that heat shock protein nuclear import factor hikeshi (HIKESHI), 
      also referred to as C11orf73, acts as a nuclear import carrier of Hsp70 under 
      heat stress conditions. The aim of the present study was to determine whether 
      knockdown (KD) of HIKESHI by small interfering RNA (siRNA) can potentiate mild HT 
      (MHT) sensitivity in human oral squamous cell carcinoma (OSCC) HSC‑3 cells. The 
      mRNA and protein expression of HIKESHI was found to be markedly suppressed in 
      HSC‑3 cells treated with siRNA for HIKESHI (siHIKE). Silencing HIKESHI 
      significantly decreased the cell viability under MHT conditions (42 C for 
      90 min). Immunocytochemical and western blot analyses clearly demonstrated that 
      Hsp70 protein translocated from the cytoplasm to the nucleus under MHT 
      conditions, and this translocation was significantly inhibited in cells treated 
      with siHIKE. Treatment of the cells with MHT transiently increased the 
      phosphorylation level of extracellular signal‑regulated kinase (ERK)2. 
      Furthermore, the phosphorylation was sustained in HIKESHI‑KD cells under MHT 
      conditions, and this sustained phosphorylation was abolished by pretreatment with 
      U0126, an inhibitor of mitogen‑activated protein kinase/ERK. In addition, U0126 
      significantly decreased the viability of cells treated with the combination of 
      HIKESHI‑KD and MHT. The data of the present study suggest that HIKESHI silencing 
      enhanced the sensitivity of human OSCC HSC‑3 cells to MHT.
FAU - Tabuchi, Yoshiaki
AU  - Tabuchi Y
AD  - Division of Molecular Genetics Research, Life Science Research Center, University 
      of Toyama, Toyama 930‑0194, Japan.
FAU - Maekawa, Keita
AU  - Maekawa K
AD  - Division of Molecular Genetics Research, Life Science Research Center, University 
      of Toyama, Toyama 930‑0194, Japan.
FAU - Torigoe, Misako
AU  - Torigoe M
AD  - Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama 930‑0194, Japan.
FAU - Furusawa, Yukihiro
AU  - Furusawa Y
AD  - Department of Liberal Arts and Sciences, Toyama Prefectural University, Toyama 
      939‑0398, Japan.
FAU - Hirano, Tetsushi
AU  - Hirano T
AD  - Division of Molecular Genetics Research, Life Science Research Center, University 
      of Toyama, Toyama 930‑0194, Japan.
FAU - Minagawa, Satsuki
AU  - Minagawa S
AD  - Division of Molecular Genetics Research, Life Science Research Center, University 
      of Toyama, Toyama 930‑0194, Japan.
FAU - Yunoki, Tatsuya
AU  - Yunoki T
AD  - Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama 930‑0194, Japan.
FAU - Hayashi, Atsushi
AU  - Hayashi A
AD  - Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama 930‑0194, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200428
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Carrier Proteins)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (hikeshi protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
SB  - IM
MH  - Blotting, Western
MH  - Carcinoma, Squamous Cell/genetics/*metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/genetics/physiology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - HSP70 Heat-Shock Proteins/genetics/metabolism
MH  - Humans
MH  - Hyperthermia/genetics/*metabolism/*pathology
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mouth Neoplasms/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC7255474
EDAT- 2020/05/08 06:00
MHDA- 2021/03/06 06:00
PMCR- 2020/04/28
CRDT- 2020/05/08 06:00
PHST- 2019/12/19 00:00 [received]
PHST- 2020/03/09 00:00 [accepted]
PHST- 2020/05/08 06:00 [pubmed]
PHST- 2021/03/06 06:00 [medline]
PHST- 2020/05/08 06:00 [entrez]
PHST- 2020/04/28 00:00 [pmc-release]
AID - ijmm-46-01-0058 [pii]
AID - 10.3892/ijmm.2020.4591 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Jul;46(1):58-66. doi: 10.3892/ijmm.2020.4591. Epub 2020 Apr 
      28.