2. Academic Validation
  3. Extracellular vesicle-derived LINC00482 induces microglial M2 polarization to facilitate brain metastasis of NSCLC

Extracellular vesicle-derived LINC00482 induces microglial M2 polarization to facilitate brain metastasis of NSCLC

  • Cancer Lett. 2023 Mar 22;216146. doi: 10.1016/j.canlet.2023.216146.
Wenwen Xu 1,  Nishant Patel 2,  Yuxia Deng 1,  Shuang Ding 3,  Tingya Wang 1,  Haijun Zhang 4
Affiliations

Affiliations

  • 1 Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China.
  • 2 Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, PR China.
  • 3 Department of Oncology, Nanjing First Hospital, Nanjing, 210001, PR China.
  • 4 Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China. Electronic address: [email protected].
PMID: 36963460 DOI: 10.1016/j.canlet.2023.216146
Abstract

Considering the crucial role of long non-coding RNAs (lncRNAs) in non-small cell lung Cancer (NSCLC), we tried to analyze the role of extracellular vesicle (EV)-derived LINC00482 in the occurrence of brain metastasis in NSCLC. LINC00482 expression was quantified in EVs isolated from serum samples of NSCLC patients (serum-EVs). Ectopic expression and depletion assays were conducted in the microglial cell line HMC3 co-cultured with serum-EVs and in xenograft mouse models of NSCLC to explore the roles of EV-carried LINC00482. LINC00482 was enriched in serum-EVs and induced M2 polarization of microglial cells HMC3 in vitro. LINC00482 competitively bound to miR-142-3p and upregulated the expression of miR-142-3p target gene TGF-β1 in HMC3 cells, thus promoting microglial M2 polarization. EV-derived LINC00482-induced M2 microglia promoted the malignant properties of NSCLC cells. In vivo data demonstrated that EVs transmitted LINC00482 to regulate the miR-142-3p/TGF-β1 axis, induce microglial M2 polarization and affect the pre-metastatic niche, thus enhancing brain metastasis of NSCLC. Overall, suppression of the expression of tumor-derived LINC00482 or LINC00482-containing EVs, may serve as an effective target for contributing to the reduction of brain metastasis of NSCLC.

Keywords

Brain metastasis; CCL16; Extracellular vesicles; LINC00482; Microglial M2 polarization; Non-small cell lung cancer; PD-L1; Pre-metastatic niche; TGF-β1; miR-142-3p.

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