MiR-148a inhibits angiogenesis by targeting ERBB3

• Published in: Journal of biomedical research 2011-05, Vol.25 (3), p.170-177
• Main Authors: Yu, Jing, Li, Qi, Xu, Qing, Liu, Lingzhi, Jiang, Binghua
• Format: Article
• Language: English
• Subjects: angiogenesis; breast cancer; ERBB3; MCF7细胞; microRNA; microRNA-148a; MIR; miRNA; Research Paper; 乳腺癌细胞; 生物学作用; 白血病病毒; 肿瘤血管生成
• ISSN: 1674-8301
• DOI: 10.1016/s1674-8301(11)60022-5

MicroRNAs （miRNAs） play an important role in carcinogenesis in various solid cancers including breast can-cer. Down-regulation of microRNA-148a （miR-148a） has been reported in certain cancer types. However, the biological role of miR-148a and its related targets in breast cancer are unknown yet. In this study, we showed that the level of miR-148a was lower in MCF7 cells than that in MCF10A cells. V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 （ERBB3） is a direct target of miR-148a in human breast cancer cells through direct binding of miR-148a to ERBB3 3’-UTR region. Overexpression of miR-148a in MCF7 cells inhibited ERBB3 expression, blocked the downstream pathway activation including activation of AKT, ERK1/2, and p70S6K1, and decreased HIF-1α expression. Furthermore, forced expression of miR-148a attenuated tumor angiogenesis in vivo. Our re-sults identify ERBB3 as a direct target of miR-148a, and provide direct evidence that miR-148a inhibits tumor an-giogenesis through ERBB3 and its downstream signaling molecules. This information would be helpful for target-ing the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the future.