Abstract
Tumor-derived exosomes (TEXs) contain enriched miRNAs, and exosomal miRNAs can affect tumor growth, including cell proliferation, metastasis, and drug resistance through cell-to-cell communication. We investigated the role of exosomal miR-1260b derived from non-small cell lung cancer (NSCLC) in tumor progression. Exosomal miR-1260b induced angiogenesis by targeting homeodomain-interacting protein kinase-2 (HIPK2) in human umbilical vein endothelial cells (HUVECs). Furthermore, exosomal miR-1260b or suppression of HIPK2 led to enhanced cellular mobility and cisplatin resistance in NSCLC cells. In patients with NSCLC, the level of HIPK2 was significantly lower in tumor tissues than in normal lung tissues, while that of miR-1260b was higher in tumor tissues. HIPK2 and miR-1260b expression showed an inverse correlation, and this correlation was strong in distant metastasis. Finally, the expression level of exosomal miR-1260b in plasma was higher in patients with NSCLC than in healthy individuals, and higher levels of exosomal miR-1260b were associated with high-grade disease, metastasis, and poor survival. In conclusion, exosomal miR-1260b can promote angiogenesis in HUVECs and metastasis of NSCLC by regulating HIPK2 and may serve as a prognostic marker for lung cancers.
Highlights
Extracellular vesicles (EVs) are lipid bilayer-enclosed particles that are secreted by almost all cell types of mammalian organisms
Exosomal miR-1260b promotes angiogenesis in human umbilical vein endothelial cells (HUVECs) by directly targeting homeodomain-interacting protein kinase-2 (HIPK2) To confirm the effect of miR-1260b on angiogenesis in HUVECs, we performed transfection with human miR-1260b or its complementary antagonist anti-miR-1260b
For the dual-luciferase assay, luciferase activities of plasmids with WT or Mut sequence of HIPK2 were assessed in HUVECs and A549 cells cotransfected with miR-1260b mimic, and Renilla luciferase activity was calculated as the luciferase activity ratio of firefly to Renilla luciferase
Summary
Extracellular vesicles (EVs) are lipid bilayer-enclosed particles that are secreted by almost all cell types of mammalian organisms. These vesicles are broadly classified into apoptotic bodies, microvesicles, and exosomes according to their size and cellular origin. Many studies have shown that exosomal miRNAs can get transferred to neighboring and distant cells [18,19,20] and play functional roles in tumor growth. Xia et al reported that the transfer of exosomal miR1260b can promote cell invasion in lung adenocarcinoma [25] and suggested the role of miR-1260b as a diagnostic or prognostic marker in various tumor types. Further validation is required for the application of miR-1260b as a clinical biomarker
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