Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4

Dong Ha Kim, Sojung Park, Hyeong Ryul Kim, Yun Jung Choi, Seon Ye Kim, Ki Jung Sung, Young Hoon Sung, Chang Min Choi, Miyong Yun, Young Su Yi, Chae Won Lee, Sang Yeob Kim, Jae Cheol Lee, Jin Kyung Rho

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Tumor-derived exosomes (TEXs) contain enriched miRNAs that act as novel non-invasive biomarkers for cancer diagnosis and play a role in cancer progression. We investigated the exosomal miRNAs that affect cancer progression in non-small cell lung cancer (NSCLC) and identified the specific molecules involved. We identified that specific miRNAs in NSCLC cell-released exosomes can modulate angiogenesis, among which miR-619-5p was the most potent inducer. RCAN1.4 was identified as a target of miR-619-5p and its suppression promoted angiogenesis. Furthermore, the suppression of RCAN1.4 induced cell proliferation and metastasis in NSCLC cells. In patients with NSCLC, the level of RCAN1.4 expression was significantly lower, and that of miR-619-5p significantly higher, in tumor than normal lung tissues. miR-619-5p expression was higher than normal in exosomes isolated from the plasma of NSCLC patients. Finally, hypoxic conditions induced miR-619-5p upload into NSCLC cell-derived exosomes. Our findings indicate that exosomal miR-619-5p promotes the growth and metastasis of NSCLCs by regulating RCAN1.4 and can serve as a diagnostic indicator for these lung cancers.

Original languageEnglish
Pages (from-to)2-13
Number of pages12
JournalCancer Letters
Volume475
DOIs
StatePublished - 10 Apr 2020

Keywords

  • Exosomal miRNAs
  • Exosome
  • Non-small cell lung cancer
  • RCAN1
  • Tumor growth

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