Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 132, Issue -, Pages 470-477Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2019.03.221
Keywords
Tumor microenvironment; Angiogenesis; VEGF
Funding
- Natural Science Foundation of Zhejiang Province [LQ16H200003, LZ17H280001]
- National Natural Science Foundation of China [81473339, 81573591]
- Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering [201510]
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Circulating exosomal microRNAs (exomiR) have been demonstrated to be novel diagnostic biomarkers for various cancers. In this study, we found that circulating exomiR-1229 levels were significantly increased in the serum exosomes of patients with colorectal cancer (CRC) and significantly associated with tumor size, lymphatic metastasis, TNM stage and poor survival. Treatment with siRNA-Drosha, siRNA-AUX and GW4869 repressed the expression of exomiR-1229 secreted from CRC cells. Both CRC-derived exosomes and exomiR-1229 mimic promoted the tubulogenesis of HUVECs, but transfection with exomiR-1229 inhibitor anta-miR-1229 significantly suppressed tube formation. Subsequently, HIPK2 was identified as a target of exomiR-1229 and responsible for the effect of exomiR-1229 on angiogenesis of HUVECs. ExorniR-1229 inhibited the protein expression of HIPK2, thereby activating VEGF pathway. Finally, anta-miR-1229 effectively inhibited tumor growth and angiogenesis in the nude mouse xenograft model. These results highlighted a novel mechanism of CRC angiogenesis and the biological roles of exomiR-1229. (C) 2019 Elsevier B.V. All rights reserved.
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