title: MiR-148a inhibits angiogenesis by targeting ERBB3.
abstract: MicroRNAs (miRNAs) play an important role in carcinogenesis in various solid cancers including breast cancer. 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 results identify ERBB3 as a direct target of miR-148a, and provide direct evidence that miR-148a inhibits tumor angiogenesis through ERBB3 and its downstream signaling molecules. This information would be helpful for targeting the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the future.
authors.affiliation: Lab of Reproductive Medicine, Department of Pathology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Liu
authors.forename: Binghua
authors.initials: B
authors.lastname: Jiang
keywords: ERBB3; angiogenesis; breast cancer; microRNA-148a
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