Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
J Cell Biochem. 2013 Jul;114(7):1457-63. doi: 10.1002/jcb.24487.
HER2 (ErbB2) has been reported to be overexpressed in 20-30% of breast cancer and confers poor survival because of high proliferation and metastasis rates. MicroRNAs are small noncoding RNAs that are responsible for the post-transcriptional regulation of target genes. We found miR-199b-5p inhibited HER2 expression by direct targeting its 3'-untranslated region (3'UTR) in breast cancer cells. In addition, miR-199b-5p inhibited HER2 downstream signaling by ERK1/2 and AKT pathways in breast cancer cells. Besides, transwell migration, wound healing, and clonogenicity were obviously inhibited by overexpression of miR-199b-5p in HER2-positive breast cancer cells. We also found that miR-199b-5p could enhance the suppression of trastuzumab on cell migration and clonogenicity. These results suggest that miR-199b-5p may have the potential to be a novel important alternative therapeutic target for HER2-positive breast cancer.
HER2（ErbB2）在 20-30%的乳腺癌中过表达，由于增殖和转移率高，预后不良。microRNAs 是小的非编码 RNA，负责靶基因的转录后调控。我们发现 miR-199b-5p 通过直接靶向乳腺癌细胞中的 3'-非翻译区（3'UTR）抑制 HER2 表达。此外，miR-199b-5p 通过 ERK1/2 和 AKT 通路抑制 HER2 下游信号。此外，过表达 miR-199b-5p 明显抑制了 HER2 阳性乳腺癌细胞的迁移、伤口愈合和集落形成能力。我们还发现 miR-199b-5p 可以增强曲妥珠单抗对细胞迁移和集落形成能力的抑制作用。这些结果表明，miR-199b-5p 可能成为治疗 HER2 阳性乳腺癌的一种新的重要替代治疗靶点。
