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MicroRNA-217 aggravates breast cancer through activation of NF1-mediated HSF1/ATG7 axis and c-Jun/ATF3/MMP13 axis

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Abstract

Application of microRNA-mediated mRNA expression in treatment of diverse cancers has been documented. The current study was explored to study the role of miR-217 in breast cancer (BC) progression and the related downstream factors. Clinical tissue samples, BC cell lines and the established xenograft models were prepared for ectopic expression and depletion experiments to discern the regulatory roles of miR-217-mediated NF1 in BC cell proliferation, metastasis and chemoresistance as well as tumorigenic ability of BC cells in nude mice. miR-217 was upregulated in BC, which was a predictor of poor prognosis of BC patients. NF1 could be targeted by miR-217. miR-217 promoted malignant characteristics of BC cells through enhancing ATF3-MMP13 interaction by inhibiting NF1. miR-217 repressed sensitivity against anti-cancer drugs by inducing autophagy of BC cells through the NF1/HSF1/ATG7 axis. Also, miR-217 could inhibit NF1 to facilitate tumorigenic ability of BC cells in vivo. Our study emphasized that miR-217 could potentially inhibit NF1 expression to activate the c-Jun, thus enhancing the expression and interaction of ATF3/MMP13 and promoting the malignant features of BC cells. Furthermore, miR-217 conferred chemoresistance on BC by enhancing BC cell autophagy, which was achieved by limiting NF1 expression to induce the HSF1/ATG7 pathway.

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The data that supports the findings of this study are available on request from the corresponding author.

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Acknowledgements

Not applicable.

Funding

This work was supported by Bao'an District Traditional Chinese Medicine Development Foundation (2020KJCX-KTYJ-12), Shenzhen Bao'an District Hospital of Traditional Chinese Medicine Pi Team Project (BAZYY20200601) and Shenzhen Bao'an District Acupuncture Clinical Research Center (BAZJ2018239).

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Authors and Affiliations

  1. Department of Acupuncture and Moxibustion, Shenzhen Bao’an Traditional Chinese Medicine Hospital, No. 25, Yu’an Second Road, Bao’an District, Shenzhen, 518000, People’s Republic of China

    Weihan Li & Peng Zhou

  2. Otorhinolaryngology Head and Neck Department, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China

    Chaojie Yang

  3. Department of Breast Surgery, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Shenzhen, 518000, People’s Republic of China

    Jingjing Li & Xiaolian Li

Authors
  1. Weihan Li
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  4. Xiaolian Li
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  5. Peng Zhou
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Contributions

WL and PZ wrote the paper and conceived and designed the experiments; CY and XL analyzed the data; WL and JL collected and provided the sample for this study. All authors have read and approved the final submitted manuscript.

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Correspondence to Peng Zhou.

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Conflict of interest

The authors declare that there are no competing interest.

Ethical approval

Informed consents were obtained from all patients prior to the study. This study was implemented under the ratification from the ethics committee of Shenzhen Bao’an Traditional Chinese Medicine Hospital (EC-2018-HS-058). All in vivo experiments were approved by Guangzhou Yongnuo Medical Laboratory Animal Center (IACUC-AEWC-F2111002) and started by referring to the recommendations in the Guide for the Care and Use of Laboratory Animals of University of Texas. Due efforts were made to limit animal pain.

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13577_2022_817_MOESM1_ESM.eps

Supplementary file2 Fig. S1. Effects of miR-217-NF1 axis on drug resistance of BC cells. A, Overexpression of miR-217 promoted the resistance of MDA-MB-453 cells to doxorubicin and cisplatin, while inhibition of miR-217 could promote its sensitivity; B, Overexpression of NF1 promoted the sensitivity of MDA-MB-453 cells to doxorubicin and cisplatin; C, Silencing HSF1 promoted the sensitivity of MDA-MB-453 cells to doxorubicin and cisplatin; In panel A, *p < 0.05 vs. MDA-MB-453 cells transduced with miR-NC; in panel B, *p < 0.05 vs. MDA-MB-453 cells transduced with oe-NC, # p < 0.05 vs. MDA-MB-453 cells transduced with miR-27-mimic + oe-NC; in panel C, # p < 0.05 vs. MDA-MB-453 cells treated with sh-NC; statistical data were measurement data, and described as mean ± standard deviation; the unpaired t test was used for comparison between two groups, the one-way analysis of variance was used for comparison among multiple groups, followed by Tukey’s post hoc test; the experiment was repeated 3 times independently. (EPS 497 KB)

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Supplementary file1 (DOCX 13 KB)

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Li, W., Yang, C., Li, J. et al. MicroRNA-217 aggravates breast cancer through activation of NF1-mediated HSF1/ATG7 axis and c-Jun/ATF3/MMP13 axis. Human Cell 36, 377–392 (2023). https://doi.org/10.1007/s13577-022-00817-y

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