机构：[1]Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, MS-8104, 12801 E. 17th Ave, Aurora, CO 80045, USA[2]Department of Hematology, Hematologic Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China四川大学华西医院[3]Cancer Research Institute and Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
The HER3 receptor functions as a major cause of drug resistance in cancer treatment. It is believed that therapeutic targeting of HER3 is required to improve patient outcomes. It is not clear whether a novel strategy with two functional cooperative miRNAs would effectively inhibit erbB3 expression and potentiate the anti-proliferative/anti-survival effects of a HER2-targeted therapy (trastuzumab) and chemotherapy (paclitaxel) on HER2-overexpressing breast cancer cells.
Combination of miR-125a and miR-205, as compared to either miRNA alone, potently inhibited expression of HER3 in HER2-overexpressing breast cancer BT474 cells. Co-expression of the two miRNAs not only reduced the levels of phosphorylated erbB3 (P-erbB3), Akt (P-Akt), and Src (P-Src), it also inhibited cell proliferation and increased cells at G1 phase. A multi-miRNA lentiviral vector - the cluster of miR-125a and miR-205 - was constructed to simultaneously express the two miRNAs in HER2-overexpressing breast cancer cells. Concurrent expression of miR-125a and miR-205 via the miRNA cluster transfection significantly enhanced trastuzumab-mediated growth inhibition and cell cycle G1 arrest in BT474 cells and markedly increased paclitaxel-induced apoptosis in another HER2-overexpressing breast cancer cell line HCC1954.
Here, we showed that functional cooperative miRNAs effectively suppressed erbB3 expression. This novel approach targeting of HER3 was able to enhance the therapeutic efficacy of trastuzumab and paclitaxel against HER2-overexpressing breast cancer.
基金：
National Institutes of Health (NIH), USA (1 R01CA201011 to BL).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|3 区生物
小类|3 区生化研究方法
最新[2023]版：
大类|3 区生物学
小类|3 区生化研究方法
第一作者：
第一作者机构：[1]Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, MS-8104, 12801 E. 17th Ave, Aurora, CO 80045, USA
通讯作者：
推荐引用方式(GB/T 7714)：
Lyu Hui,Huang Jingcao,He Zhimin,et al.Targeting of HER3 with Functional Cooperative miRNAs Enhances Therapeutic Activity in HER2-Overexpressing Breast Cancer Cells.[J].Biological procedures online.2018,20:16.doi:10.1186/s12575-018-0081-x.
APA：
Lyu Hui,Huang Jingcao,He Zhimin&Liu Bolin.(2018).Targeting of HER3 with Functional Cooperative miRNAs Enhances Therapeutic Activity in HER2-Overexpressing Breast Cancer Cells..Biological procedures online,20,
MLA：
Lyu Hui,et al."Targeting of HER3 with Functional Cooperative miRNAs Enhances Therapeutic Activity in HER2-Overexpressing Breast Cancer Cells.".Biological procedures online 20.(2018):16
