6-Formylindolo[3,2-b]carbazole (FICZ) Enhances The Expression of Tumor Suppressor miRNAs, miR-22, miR-515-5p, and miR-124-3p in MCF-7 Cells


Keivan Mobini, Ph.D, 1Elham Banakar, Pharm.D, 1Gholamhossein Tamaddon, Ph.D, 2Afshin Mohammadi-Bardbori, Ph.D., 1,*
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
*Corresponding Address: P.O.Box: 1583-71345 Department of Pharmacology and Toxicology School of Pharmacy Shiraz University of Medical Sciences Shiraz Iran Email:toxicology@sums.ac.ir
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Abstract

Objective

microRNAs (miRNAs) play bifunctional roles in the initiation and progression of cancer, and recent evidence has confirmed that unusual expression of miRNAs is required for the progress of breast cancer. The regulatory role of aryl hydrocarbon receptor (AhR) and its endogenous ligand, 6-formylindolo[3,2-b]carbazole (FICZ) on the expression of tumor suppressor miRNAs, miR-22, miR-515-5p and miR-124-3p, as well as their association with the estrogen receptor alpha (ERα) were the aims of this study.

Materials and Methods

In this experimental study, the expression levels of miR-22, miR-515-5p, miR-124-3p and miR-382-5p in MCF-7 cells were determined using the quantificational real time polymerase chain reaction (qRT-PCR) assay.

Results

Our results revealed that miR-22, miR-515-5p, and miR-124-3p expressions were significantly increased in cells transfected with ERα siRNA. Our data also showed that miR-22, miR 515-5p, and miR-124-3p expression levels were significantly increased following FICZ treatment. Here, we found that AhR/ERα cross-talk plays a critical role in the expression of miR-22, miR-515-5p and miR-124-3p in MCF-7 cells.

Conclusion

Overall, our data demonstrated that FICZ, as an AhR agonist could induce the expression of tumor suppressor miRNAs, miR-22, miR-515-5p, and miR-124-3p; thus, FICZ might be regarded as a potential therapeutic agent for breast cancer treatment.