2. Academic Validation
  3. Exosomes deliver lncRNA DARS-AS1 siRNA to inhibit chronic unpredictable mild stress-induced TNBC metastasis

Exosomes deliver lncRNA DARS-AS1 siRNA to inhibit chronic unpredictable mild stress-induced TNBC metastasis

  • Cancer Lett. 2022 Sep 1;543:215781. doi: 10.1016/j.canlet.2022.215781.
Xinli Liu 1,  Ge Zhang 1,  Tongyao Yu 1,  Jinliang He 1,  Jie Liu 1,  Xiaoxia Chai 1,  Gang Zhao 2,  Dachuan Yin 3,  Chenyan Zhang 4
Affiliations

Affiliations

  • 1 Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China.
  • 2 The First Hospital of Jilin University, Changchun, 130021, China. Electronic address: roger740820@163.com.
  • 3 Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China. Electronic address: yindc@nwpu.edu.cn.
  • 4 Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China. Electronic address: zhangchenyan@nwpu.edu.cn.
PMID: 35688263 DOI: 10.1016/j.canlet.2022.215781
Abstract

Triple-negative breast Cancer (TNBC) is a rapidly recurring and highly metastatic malignancy with high heterogeneity and chemoradiotherapy resistance. Chronic unpredictable mild stress (CUMS) can induce the occurrence of tumors and enhance lymphatic infiltration and distant metastasis through direct interaction with the sympathetic nervous system; however, its relevance in TNBC is yet to be clarified. In this study, DARS-AS1, a newly reported CUMS-responsive lncRNA, was found to be enriched in TNBC clinical tumors and cells and positively correlated with late clinical stage in patients with TNBC. DARS-AS1 overexpression significantly enhanced the migration and invasion of TNBC tumors by inhibiting miR-129-2-3p and upregulated CDK1 to activate the NF-κB/STAT3 signaling pathway both in vitro and in vivo. Treatment with DARS-AS1 siRNA-loaded exosomes (EXOs) substantially slowed CUMS-induced TNBC cell growth and liver metastasis. Therefore, DARS-AS1 represents a potential therapeutic target for metastatic TNBC, and EXOs may serve as siRNA delivery carriers in clinical therapy.

Keywords

Breast cancer liver metastasis (BCLM); CDK1; Chronic unpredictable mild stress (CUMS); Long non-coding RNA DARS-AS1 (DARS-AS1); siRNA-loaded exosomes.

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