Apoptotic effects of valproic acid on miR-34a, miR-520h and HDAC1 gene in breast cancer

• Published in: Life sciences (1973) Vol. 269; p. 119027
• Main Authors: Injinari, Nastaran, Amini-Farsani, Zeinab, Yadollahi-Farsani, Mahtab, Teimori, Hossein
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.03.2021; Elsevier BV
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Bioinformatics; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Survival - drug effects; Epigenetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Regulatory Networks; HDAC1 gene; Histone deacetylase; Histone Deacetylase 1 - genetics; Histone Deacetylase 1 - metabolism; Humans; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Medical research; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Peroxidation; Reactive Oxygen Species - metabolism; ROC Curve; Valproic acid; Valproic Acid - pharmacology; HDAC1 gene; miRNA; Breast cancer; Valproic acid; Apoptosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119027

Identifying miRNAs involved in cancer and devising strategies to control their expression is a new therapeutic approach. Valproic acid (VPA) has attracted a lot of interest in cancer research. We evaluated the impact of VPA on the expression of miR-34a, miR-520h, and their target gene histone deacetylase 1 (HDAC1), as well as their relationship with apoptosis in breast cancer. First, through bioinformatics analyses, the possible target genes of miR-34a and miR-520h and their roles in apoptosis regulation were investigated. Then, miR-34a, miR-520h, and HDAC1 gene expression in tissues of breast cancer patients were determined using the qRT-PCR method. The anticancer impact of VPA on apoptosis and the expression levels of miR-34a, miR-520h, and HDAC1 gene were measured in MCF-7 and MDA-MB-231 cell lines. The bioinformatics analyses indicated that miR-34a and miR-520h might make a unique contribution in regulating the apoptosis pathway. The relative expression of miR-34a and miR-520h significantly decreased in cancer tissues, while the relative expression of HDAC1 increased. In the in vitro study, VPA led to apoptosis induction and increased lipid peroxidation products in breast cancer cells. Moreover, VPA increased the expression of miR- 34a and miR-520h and decreased HDAC1 expression in MCF-7 cells. In MDA-MB-231 cells, VPA decreased the expression of these miRNAs and increased the expression of HDAC1. It can be concluded that miR-34a and miR-520h are implicated in the apoptosis pathways, and thus, VPA can recruit as a possible option in breast cancer research due to its interference with epigenetic processes. [Display omitted]