Curcumin as an Epigenetic Modulator: Suppression of Breast Cancer via the Hsa_circ_0001946/MiR-7-5p/Target Gene Axis

<i>Background and Objectives</i>: Curcumin is a turmeric-derived polyphenol, and it has shown anticancer potential in various cancers, including breast cancer (BC). Nevertheless, the molecular mechanisms underlying its effects remain incompletely defined. Hsa_circ_0001946 (CDR1as) is a circular RNA (circRNA) that promotes tumor progression by competitively inhibiting microRNA-7-5p (miR-7-5p) in BC. This study investigated whether curcumin regulates the hsa_circ_0001946/miR-7-5p/target gene axis in BC progression. <i>Materials and Methods</i>: BC cell lines (MCF-7 and T47D) and a non-cancerous human mammary epithelial cell line (MCF-10A) were treated with curcumin or transfected with circ_0001946 siRNA or miR-7-5p mimic. Cell proliferation, migration, apoptosis, and protein expression were analyzed by CVDK-8 analysis, a wound healing assay, and flow cytometry, respectively. Also, protein expression levels were quantified via Western blotting. In vitro and in silico findings were further validated by analyzing tumor and adjacent normal tissues from 65 luminal BC patients. <i>Results</i>: Curcumin inhibited the proliferation and migration of MCF-7 and T47D cells in a dose-dependent manner. Knockdown of hsa_circ_0001946 or overexpression of miR-7-5p significantly suppressed proliferation and migration and enhanced apoptosis in BC cells compared to the negative controls. Curcumin treatment led to the knockdown of hsa_circ_0001946, the overexpression of miR-7-5p, and the downregulation of hsa_circ_0001946, <i>CKS2</i>, <i>TOP2A</i>, and <i>PARP1</i>, while it upregulating miR-7-5p. The Western blot confirmed reduced CKS2 protein levels after curcumin treatment. The expression of both hsa_circ_0001946 and <i>CKS2</i> was significantly upregulated in tumor tissues compared to that of matched adjacent normal tissues, whereas that of miR-7-5p was markedly downregulated. <i>Conclusions</i>: This preliminary study shows that curcumin suppresses BC tumorigenesis by modulating the hsa_circ_0001946/miR-7-5p/target gene axis. While these findings suggest a novel regulatory pathway and potential therapeutic targets, further in vivo validation and clinical trials are required to determine the translational relevance of curcumin in BC therapy.