PMID- 30942430
OWN - NLM
STAT- MEDLINE
DCOM- 20190826
LR  - 20211204
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 54
IP  - 6
DP  - 2019 Jun
TI  - Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation 
      of miR-99a-5p in human bladder cancer cells.
PG  - 2106-2116
LID - 10.3892/ijo.2019.4763 [doi]
AB  - Benzyl isothiocyanate (BITC) is known for its pharmacological properties against 
      malignant neoplasm, including bladder cancer (BC). The current study investigated 
      microRNAs (miRNA or miR) expression profiles with an emphasis on the role of 
      miR‑99a‑5p in BITC‑treated BC cells. A quantitative polymerase chain reaction 
      (qPCR) microarray containing 79 aberrantly expressed miRNAs in BC was used to 
      detect miRNA expression in BITC‑treated cells. Several dysregulated miRNAs were 
      identified and further confirmed using miRNA stem‑loop reverse 
      transcription (RT)‑qPCR in 5637 cells. Insulin‑like growth factor 1 
      receptor (IGF1R), fibroblast growth factor receptor 3 (FGFR3) and mammalian 
      target of rapamycin (mTOR) expression were determined by RT‑qPCR and western 
      blotting. Cell viability was evaluated using WST‑1 reagent and apoptosis was 
      monitored by determining the levels of cleaved‑poly ADP‑ribose polymerase and 
      cleaved‑caspase‑3. BITC treatment significantly upregulated miR‑99a‑5p levels in 
      a dose‑dependent manner. miR‑99a‑5p overexpression decreased IGF1R, mTOR and 
      FGFR3 expression, predicted targets of miR‑99a‑5p. In addition, antisense 
      miR‑99a‑5p sequences inhibited BITC‑induced miR‑99a‑5p overexpression, resulting 
      in the restoration of protein expression and decreased cell viability. The 
      current study identified multiple miRNAs responsive to BITC treatment, including 
      miR‑99a‑5p. In addition, the induction of miR‑99a‑5p decreased IGF1R, mTOR and 
      FGFR3 expression in BITC‑treated BC cells. The current study provided novel 
      insight into the antitumor mechanism by which BITC restores miR‑99a‑5p expression 
      and decreases cancer cell survival.
FAU - Lin, Ji-Fan
AU  - Lin JF
AD  - Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan, 
      R.O.C.
FAU - Tsai, Te-Fu
AU  - Tsai TF
AD  - Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei 
      City 242, Taiwan, R.O.C.
FAU - Lin, Yi-Chia
AU  - Lin YC
AD  - Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei 
      City 242, Taiwan, R.O.C.
FAU - Chen, Hung-En
AU  - Chen HE
AD  - Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei 
      City 242, Taiwan, R.O.C.
FAU - Chou, Kuang-Yu
AU  - Chou KY
AD  - Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei 
      City 242, Taiwan, R.O.C.
FAU - Hwang, Thomas I-Sheng
AU  - Hwang TI
AD  - Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei 
      City 242, Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
DEP - 20190326
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antineoplastic Agents)
RN  - 0 (IGF1R protein, human)
RN  - 0 (Isothiocyanates)
RN  - 0 (MIRN99 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, Somatomedin)
RN  - 871J6YOR8Q (benzyl isothiocyanate)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Apoptosis/drug effects/genetics
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/genetics
MH  - Drug Screening Assays, Antitumor
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Isothiocyanates/*pharmacology/therapeutic use
MH  - MicroRNAs/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptor, Fibroblast Growth Factor, Type 3/genetics
MH  - Receptor, IGF Type 1
MH  - Receptors, Somatomedin/genetics
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Up-Regulation/drug effects
MH  - Urinary Bladder Neoplasms/*drug therapy/genetics/pathology
EDAT- 2019/04/04 06:00
MHDA- 2019/08/27 06:00
CRDT- 2019/04/04 06:00
PHST- 2018/05/29 00:00 [received]
PHST- 2018/11/26 00:00 [accepted]
PHST- 2019/04/04 06:00 [pubmed]
PHST- 2019/08/27 06:00 [medline]
PHST- 2019/04/04 06:00 [entrez]
AID - 10.3892/ijo.2019.4763 [doi]
PST - ppublish
SO  - Int J Oncol. 2019 Jun;54(6):2106-2116. doi: 10.3892/ijo.2019.4763. Epub 2019 Mar 
      26.