Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells

Yusuke Matsuura, Hiroshi Wada, Hidetoshi Eguchi, Kunihito Gotoh, Shogo Kobayashi, Mitsuru Kinoshita, Masahiko Kubo, Koji Hayashi, Yoshifumi Iwagami, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Koichi Kawamoto, Yutaka Takeda, Masahiro Tanemura, Koji Umeshita, Yuichiro Doki, Masaki Mori

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Abstract

Purpose: In this study, we aim to clarify whether exosomes secreted from hepatocellular carcinoma (HCC) cells under hypoxia affect angiogenesis in endothelial cells. Methods: Exosomes derived from human liver cancer cell lines were cultured under hypoxic or normoxic conditions for 24 h, isolated using ExoQuick-TC ® , and co-cultured with HUVECs to evaluate angiogenic activity. We also evaluated the expression of miR-155 in the exosomes from 40 patients with HCC. Results: Exosomes under hypoxia remarkably enhanced tube formation of HUVECs. Both cellular and exosomal miR-155 were significantly up-regulated under hypoxic conditions. Knockdown of miR-155 in HCC cells attenuated the promotion of tube formation by exosomes under hypoxia in HUVECs, and high expression of exosomal miR-155 in preoperative plasma was significantly correlated with early recurrence. Conclusion: These results suggest that exosomes derived from HCC cells under hypoxia induce tube formation of HUVECs and that exosomal miR-155 may affect angiogenic activity in HCC.

Original languageEnglish
Pages (from-to)792-802
Number of pages11
JournalDigestive Diseases and Sciences
Volume64
Issue number3
DOIs
Publication statusPublished - Mar 15 2019

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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