Journal
LIFE SCIENCES
Volume 278, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119495
Keywords
Pancreatic cancer; Long non-coding RNA colon cancer-associated; transcript-1; MicroRNA-138-5p; High mobility group A1; Angiogenesis; Exosomes; Human microvascular endothelial cells
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The study reveals that exosomal CCAT1 derived from PANC-1 cells enhances angiogenesis of HUVECs by regulating the miR-138-5p/HMGA1 axis.
Objective: Pancreatic cancer (PC) cells-derived exosomes could mediate angiogenesis of human microvascular endothelial cells (HUVECs) in PC. Considering that, this research was implemented to figure out the concrete role of PC cells-derived exosomal long non-coding RNA colon cancer-associated transcript-1 (CCAT1) in PC with its regulation on microRNA-138-5p/high mobility group A1 (miR-138-5p/HMGA1) axis. Methods: PC tissues and normal tissues were resected. PC cells (PANC-1) were interfered with plasmids to change CCAT1 and/or miR-138-5p expression. Exosomes were isolated from PANC-1 cells and co-cultured with HUVECs. The proliferation and apoptosis of PANC-1 and HUVECs were examined. The angiogenic ability of HUVECs was tested in vivo in xenografted tumors and in vitro. CCAT1, miR-138-5p and HMGA1 expression were determined, as well as their interactions. Results: CCAT1 and HMGA1 expression were raised while miR-138-5p expression was reduced in PC. Silencing CCAT1 disrupted cell proliferation and stimulated apoptosis of PANC-1 cells. Knocked down CCAT1 from PANC1 cells-derived exosomes promoted apoptosis and repressed proliferation of HUVECs. Down-regulated/upregulated CCAT1 from PANC-1 cells-derived exosomes destroyed/enhanced the angiogenic ability of HUVECs in vivo and in vitro. CCAT1 mediated HMGA1 through competitively binding to miR-138-5p. Overexpression of miR-138-5p antagonized the effects of up-regulated CCAT1 on angiogenesis of HUVECs in vitro. Conclusion: It is informative that PANC-1 cells-derived exosomal CCAT1 strengthens angiogenesis of HUVECs through binding to miR-138-5p to elevate HMGA1 expression.
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