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. 2022 Jul;22(7):655-662.
doi: 10.1007/s12012-022-09748-4. Epub 2022 May 7.

microRNA miR-133a as a Biomarker for Doxorubicin-Induced Cardiotoxicity in Women with Breast Cancer: A Signaling Pathway Investigation

Michelle Teodoro Alves  1   2 , Izabela Mamede Costa Andrade da Conceição  3 , Angélica Navarro de Oliveira  4 , Heloísa Helena Marques Oliveira  5 , Cintia Esteves Soares  6 , Adriano de Paula Sabino  1 , Luciana Maria Silva  5 , Ricardo Simões  7 , Marcelo Rizzatti Luizon  3 , Karina Braga Gomes  8   9
Affiliations

microRNA miR-133a as a Biomarker for Doxorubicin-Induced Cardiotoxicity in Women with Breast Cancer: A Signaling Pathway Investigation

Michelle Teodoro Alves et al. Cardiovasc Toxicol. 2022 Jul.

Abstract

Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control). To further explore the potential roles of these circulating miRNA in cardiotoxicity, we searched the miRTarBase for experimentally validated miRNA-target interactions and performed a functional enrichment analysis based on those interactions. miR-133a was significantly upregulated in case compared to control group. The most relevant pathway regulated by miR-133a was ErbB2 signaling, whose main genes involved are EGFR, ERBB2, and RHOA, which are possibly downregulated by miR133a. The other miRNAs did not show significant differential expression when compared on both groups. The data suggest that miR-133a is associated with DOX-based cardiotoxicity during chemotherapy in breast cancer patients through ErbB2 signaling pathway. Moreover, miR-133a may be a future marker of DOX-induced cardiotoxicity in women with breast cancer.

Keywords: Breast cancer; Cardiotoxicity; Doxorubicin; microRNA.

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