Journal
CELL DEATH & DISEASE
Volume 12, Issue 8, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-04024-9
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Funding
- National Research Foundation of Korea (NRF) - Korean government [2019R1C1C1007262, 2019R1A2C2006054]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HA16C0023]
- Asan Institute for Life Sciences, Seoul, Korea [2021IP0058]
- National Research Foundation of Korea [2019R1A2C2006054, 2019R1C1C1007262] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Exosomal miR-1260b promotes angiogenesis in HUVECs and metastasis in NSCLC by targeting HIPK2, and may serve as a potential prognostic marker for lung cancer.
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.
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