MicroRNAs-141 and 200a regulate the SVCT2 transporter in bone marrow stromal cells

• Published in: Molecular and cellular endocrinology 2015-07, Vol.410, p.19-26
• Main Authors: Sangani, Rajnikumar, Periyasamy-Thandavan, Sudharsan, Kolhe, Ravindra, Bhattacharyya, Maryka H., Chutkan, Norman, Hunter, Monte, Isales, Carlos, Hamrick, Mark, Hill, William D., Fulzele, Sadanand
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Animals; ascorbic acid; Ascorbic Acid - metabolism; BMSCs; bone formation; bone marrow; Cell Differentiation; Cells, Cultured; gene expression; Gene Expression Regulation; genes; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; messenger RNA; Mice; microRNA; MicroRNAs - genetics; miRNA-141; miRNA-200a; non-coding RNA; Osteogenesis; Osteogenic differentiation; sodium; Sodium-Coupled Vitamin C Transporters - genetics; stromal cells; SVCT2; Vitamin C transporter
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2015.01.007

•Mouse BMSCs express miR-141 and miR-200a.•MiR-141 and miR-200a repressed SVCT2 expression by targeting the 3′-UTR of mRNA.•MiR-141 and miR-200a decrease osteogenic differentiation.•MiRNA inhibitors (antagomir) of miR-141 and miR-200a increased SVCT2 and osteogenic gene expression. Vitamin C is a micro-nutrient which plays an important role in bone marrow stromal cell (BMSCs) differentiation to osteogenesis. This vitamin is transported into the BMSCs through the sodium dependent vitamin C transporter 2 (SVCT2). We previously reported that knockdown of the SVCT2 transporter decreases osteogenic differentiation. However, our understanding of the post-transcriptional regulatory mechanism of the SVCT2 transporter remains poor. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate the messenger RNAs of protein-coding genes. In this study, we aimed to investigate the impact of miR-141 and miR-200a on SVCT2 expression. We found that mouse BMSCs expressed miR-141 and miR-200a and repressed SVCT2 expression at the functional level by targeting the 3′-untranslated region of mRNA. We also found that miR-141 and miR-200a decreased osteogenic differentiation. Furthermore, miRNA inhibitors increased SVCT2 and osteogenic gene expression in BMSCs. Taken together, these results indicate that both miRNAs are novel regulators of the SVCT2 transporter and play an important role in the osteogenic differentiation of BMSCs.