Targeting of HER3 with Functional Cooperative miRNAs Enhances Therapeutic Activity in HER2-Overexpressing Breast Cancer Cells.
Targeting of HER3 with Functional Cooperative miRNAs Enhances Therapeutic Activity in HER2-Overexpressing Breast Cancer Cells.
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DOI：
10.1186/s12575-018-0081-x
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发表时间：
2018
影响因子：
6.4
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Lyu H;Huang J;He Z;Liu B
HER3受体作为癌症治疗中耐药性的主要原因发挥作用。据信，需要HER3的治疗靶向来改善患者结果。目前尚不清楚具有两种功能性协同miRNA的新策略是否会有效抑制erbB3表达并增强HER2靶向治疗（曲妥珠单抗）和化疗（紫杉醇）对HER2过表达乳腺癌细胞的抗增殖/抗存活作用。与单独的任一种miRNA相比，miR-125a和miR-205的组合有效地抑制HER2过表达乳腺癌BT474细胞中HER3的表达。这两种miRNAs的共表达不仅降低了磷酸化erbB3（P-erbB3）、Akt（P-Akt）和Src（P-Src）的水平，还抑制了细胞增殖并增加了G1期细胞。构建了一个多miRNA慢病毒载体-miR-125a和miR-205的簇-以在HER2过表达的乳腺癌细胞中同时表达这两种miRNA。通过miRNA簇转染同时表达miR-125a和miR-205显著增强了BT474细胞中曲妥珠单抗介导的生长抑制和细胞周期G1期阻滞，并显著增加了另一种HER2过表达乳腺癌细胞系HCC 1954中紫杉醇诱导的凋亡。在这里，我们发现功能性协同miRNA有效抑制erbB3表达。这种靶向HER3的新方法能够增强曲妥珠单抗和紫杉醇对HER2过表达乳腺癌的治疗效果。本文的在线版本（10.1186/s12575 - 018 - 0081-x）包含补充材料，可供授权用户使用。
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. The online version of this article (10.1186/s12575-018-0081-x) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Bader AG;Brown D;Winkler M
通讯作者：
Winkler M
DOI：
10.1016/j.omtn.2017.06.005
发表时间：
2017-09-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chakraborty C;Sharma AR;Sharma G;Doss CGP;Lee SS
通讯作者：
Lee SS
影响因子：
7.3
作者：
Amin DN;Campbell MR;Moasser MM
通讯作者：
Moasser MM
影响因子：
5.8
作者：
Adams BD;Parsons C;Slack FJ
通讯作者：
Slack FJ
影响因子：
11.2
作者：
Lee-Hoeflich, Si Tuen;Crocker, Lisa;Stern, Howard M.
通讯作者：
Stern, Howard M.