Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation of miR-99a-5p in human bladder cancer cells

  • Authors:
    • Ji-Fan Lin
    • Te-Fu Tsai
    • Yi-Chia Lin
    • Hung-En Chen
    • Kuang-Yu Chou
    • Thomas I-Sheng Hwang
  • View Affiliations

  • Published online on: March 26, 2019     https://doi.org/10.3892/ijo.2019.4763
  • Pages: 2106-2116
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Abstract

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.

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Copy and paste a formatted citation
APA
Lin, J., Tsai, T., Lin, Y., Chen, H., Chou, K., & Hwang, T. (2019). Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation of miR-99a-5p in human bladder cancer cells. International Journal of Oncology, 54, 2106-2116. https://doi.org/10.3892/ijo.2019.4763
MLA
Lin, J., Tsai, T., Lin, Y., Chen, H., Chou, K., Hwang, T."Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation of miR-99a-5p in human bladder cancer cells". International Journal of Oncology 54.6 (2019): 2106-2116.
Chicago
Lin, J., Tsai, T., Lin, Y., Chen, H., Chou, K., Hwang, T."Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation of miR-99a-5p in human bladder cancer cells". International Journal of Oncology 54, no. 6 (2019): 2106-2116. https://doi.org/10.3892/ijo.2019.4763