Abstract 2785: Effects of melatonin and 17β-estradiol on the miR-222-3p's expression and activity in IDCs cells

Abstract Background: The DICER gene encodes a protein that is required for RNA interference and microRNA (miRNA) synthesis. It is known that miRNAs have a substantial impact on cancer origin and progression, and they are deeply involved in the posttranscriptional regulation of genes expression. A growing body of evidence indicates that the oncomiR miR-222-3p overexpression promotes proliferation, migration, invasion, and metastasis of breast cancer (BC) cells as well as chemoresistance, by the regulation of its target genes. However, in this circuit, the miR-222 negatively regulates the expression of DICER, which can be involved with tumor malignant behavior. In an attempt to modulate the miR-222 expression, we treated invasive ductal carcinoma (IDC) cells with melatonin (Mel), which exerts anti-tumor actions by regulating miRNA expression and may protect against BC. In addition, we stimulated the IDC cells with 17β-estradiol (E2) to mimic the hormonal conditions. Hence, our goal was to evaluate the miR-222 expression under the effects of Mel and E2 treatments in IDC cells and to assess the expression of its target gene DICER. Methods: MCF7 and MDA-MB231 cell lines treatments were performed with 3000 µM Mel and 100 nM E2, and the two drugs were combined (M+E2) and were replaced daily. After the treatment, the RNA was extracted and the reverse transcription was performed. Expression of miR-222 and DICER were assessed by RT-PCR. Data analysis was performed with ExpressionSuite Software v1.3. Results: miR-222 showed a significant decrease with Mel (fold: 0.701) and M+E2 (fold: 0.829) treatments in MCF7 cells, compared to control. However, the E2 treatment did not significantly affect the miR-222 expression. Inversely, DICER expression was increased with suppression of miR-222 after the treatments, both Mel (fold: 1.436) and M+E2 (fold: 1.368). After the E2 treatment, DICER presented low expression levels (fold: 0.720), compared to control. In MDA cells, the expression levels of miR-222 were increased after Mel (fold: 1.095) and M+E2 (fold: 1.109) treatments, compared to control. miRNA-222 showed a slight reduction in expression with E2 treatment (fold: 0.856). Nonetheless, DICER did not present differences of expression. Although Mel and M+E2 led to a greater expression of miR-222, these treatments also increased the expression of DICER (Mel fold: 2.011 and M+E2 fold: 1.979). Conclusion: These data revealed that miR-222 contributes to the tumorigenicity of IDC through the down-regulation of DICER in MCF7 cells. In addition, the anticancer effect of Mel modulates the critical expression of miR-222-3p and its target DICER in IDC cells. Supported by: FAPESP 2022/04174-2 and 2018/24224-9 Citation Format: Bruna Cristine De Almeida, Kelly Pedrozo Ferreira, José Maria Soares-Júnior, Juciara Costa Silva, Katia Candido Carvalho, Edmund Chada Baracat. Effects of melatonin and 17β-estradiol on the miR-222-3p's expression and activity in IDCs cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2785.