Breast Cancer: Impact of Protumoral Dietary Components and Patterns on MicroRNA Regulation

Abstract

MicroRNAs (miRs) are involved in the regulation of gene expression and exhibit specific dysregulation in various types of cancer (Oncogenic and Tumor Suppressor miRs). Given that dietary habits may play a role in cancer development, this study aimed to investigate the effect of protumoral dietary patterns on the expression of miRs commonly dysregulated in breast cancer. The study examined the effect of dietary components fructose (F), palmitic acid (PA), and a combination of both (F+PA) on miR expression in cultures of MCF7 breast cancer cells and Carcinoma-Associated Fibroblasts F88 (CAF-F88). It also analyzed miR expression in a murine model of breast cancer in the context of diets rich in fructose (PBA), high in fat (PCS), and a combination of both (PBA+PCS).

miRs were extracted from samples obtained from culture, serum, and tumor tissue. The expression of miRs was determined through reverse transcription and quantitative polymerase chain reaction (RT-qPCR), using Taqman-specific primers and probes for Oncogenic miRs miR-21, miR-155, miR-10b, and miR-210, and the Tumor Suppressor miRs miR-let7a and miR-195. Each experiment consisted of three biological replicates, and each reaction was performed in triplicate. One-way ANOVA tests followed by Bonferroni's test were conducted using the GraphPad Prism 9.00 software (statistical significance established at P<0.05).

Overexpression of Oncogenic miRs and a decrease in the expression of Tumor Suppressor miRs were observed. In MCF7 cells, miR expression was mainly affected by the F+PA treatment. In CAF-F88 cells, overexpression of Oncogenic miRs was observed with PA treatment, and a decrease in Tumor Suppressor miRs was detected with F+PA treatment. In the serum and tumor of the murine experimental model, a significant increase in the OncomiR miR-21 and a decrease in the Tumor Suppressor miR-Let7a were observed in the group treated with the PBA+PCS diet.

The observed changes in the expression of miRs commonly dysregulated in breast cancer demonstrate the involvement of miRs as one of the underlying molecular regulatory mechanisms that may promote tumor development and proliferation in the context of protumoral diets and nutritional patterns.