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miR-182 regulates trastuzumab resistance by targeting MET in breast cancer cells

Cancer Gene Therapy volume 26, pages 1–10 (2019)Cite this article

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Abstract

It has been found that microRNAs (miRNAs) play a key role in drug resistance. The purpose of the current study was to investigate the function of miR-182 in trastuzumab resistance in breast cancer cells. The results showed that both breast cancer SKBR3 trastuzumab-resistant cells (SKBR3/TR) and BT474 trastuzumab-resistant cells (BT474/TR) were associated with miR-182 downregulation compared with their parental cells. Ectopic expression of the miR-182 mimic inhibited trastuzumab resistance, decreasing the invasion and migration of these trastuzumab-resistant cells. However, the miR-182 inhibitor increased trastuzumab resistance, cell invasion, and migration in the parental cells. In addition, MET is a directly targeted gene of miR-182 in breast cancer cells. MET knockdown showed an inhibitory effect of trastuzumab resistance on trastuzumab-resistant cells. In contrast, MET overexpression in SKBR3 cells produced an effect that promotes resistance to trastuzumab. Moreover, we revealed that overexpression of miR-182 reduced trastuzumab resistance in trastuzumab-resistant cells due in part to MET/PI3K/AKT/mTOR signaling pathway inactivation. Furthermore, miR-182 could also sensitize SKBR3/TR cells to trastuzumab in vivo. In conclusion, our results suggest that the activation of miR-182 or inactivation of its target gene pathway could be used as a new method to reverse trastuzumab resistance in breast cancer.

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Authors and Affiliations

  1. Department of Immunology, China Medical University, Shenyang, China

    Dan Yue

  2. Laboratory Medicine Department, Sheng Jing Hospital of China Medical University, 36 Sanhao St, Heping Qu, 110003, Shenyang, China

    Dan Yue & Xiaosong Qin

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  1. Dan Yue
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Correspondence to Xiaosong Qin.

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Yue, D., Qin, X. miR-182 regulates trastuzumab resistance by targeting MET in breast cancer cells. Cancer Gene Ther 26, 1–10 (2019). https://doi.org/10.1038/s41417-018-0031-4

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