Benzyl isothiocyanate promotes miR‐99a expression through ERK/AP‐1‐dependent pathway in bladder cancer cells

Abstract

Benzyl isothiocyanate (BITC), a bioactive natural product present in cruciferous vegetables, has been proved to prevent cancer progression through various mechanisms.In our previous report, we proved that BITC exhibits antitumor effects in bladder cancer by suppressing IGF1R, FGFR3, and mTOR, which is mediated by miR-99a expression. In this study, we identified the signal pathway involved in regulating miR-99a expression after BITC exposure in bladder cancer. Treatment with different BITC concentrations resulted in induction of miR-99a expression in bladder cancer cell lines. Activation of extracellular signal-regulated protein kinase (ERK) and c-jun Nterminal kinase was observed in bladder cancer after BITC treatment for 24 hours.Interestingly, by using a chemical inhibitor of candidate pathways, we found that only the ERK signal pathway is required for miR-99a expression. Furthermore, we evaluated the transcription factor that may contribute to miR-99a expression in response to BITC treatment. The results indicated that c-Jun/AP-1 was activated after BITC treatment. Moreover, we confirmed c-Jun/AP-1 activation through immunofluorescence and the luciferase reporter assay. The results showed that BITC treatment markedly improved nuclear translocation of c-Jun/AP-1 and luciferase activity dose dependently. Finally, pretreatment with the ERK inhibitor U0126 diminished c-Jun phosphorylation and transcriptional activation, suggesting that BITC elicits ERK/c-Jun signal transduction, which is responsible for miR-99a expression in bladder cancer. The present work identifies the mechanism involved in upregulation miR-99a after BITC treatment, which provides an explanation for BITC biological function in our previous work. K E Y W O R D SAP-1, BITC, bladder cancer, ERK, miR-99a

WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression

“…As a member of the miR-99 family, miR-99a-3p is transcribed from the 21 region of the long arm of chromosome 21. miR-99 is expressed at low levels in a variety of human malignant tumors. It participates in the occurrence and development of a variety of urinary tumors [7], head and neck squamous cell carcinoma [8], liver cancer [9] and ovarian cancer [10], and has certain signi cance in the early diagnosis and staging of tumors [11].…”

Thrombospondin‐4 promotes bladder cancer cell migration and invasion via MMP2 production

“…qRT–PCR assays were conducted in triplicate on a StepOnePlus sequence detection system (Thermo Fisher Scientific). The cycling conditions were conducted under identical conditions as those in a previous study 23 . The threshold was set above the non‐template control background and within the linear phase of target gene amplification to calculate the cycle number at which the transcript is detected (denoted C T ).…”

Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver

“…is compound (10 mg/kg, i.p, 7 days) showed cardioprotective and anti-inflammatory effects due to an increase in the expression of miRNA-29a that had been suppressed by lipopolysaccharide (LPS, 10 mg/kg, i.p) in mice cardiomyocytes [118]. Antrocin [119], benzyl isothiocyanate [120], capsaicin [121], curcumin [122], quercetin [123], genistein [124], ginsenoside [125], emodin [126], oleuropein [127], resveratrol [128], and other secondary metabolites that could affect the regulation of miRNAs' expression and their natural sources are shown in Table 1. Evidence-Based Complementary and Alternative Medicine Achillea millefolium (Asteraceae) [143] Evidence-Based Complementary and Alternative Medicine [154].…”