Wei Han1, Qiuman Sulidankazha2, Xiaohan Nie2, Reheman Yilidan2, Kunzeng Len2. 1. Department of Pancreatic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi Municipality 830054, Xinjiang, China. Electronic address: Hanwei2334@outlook.com. 2. Department of Pancreatic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi Municipality 830054, Xinjiang, China.
Abstract
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 PANC-1 cells-derived exosomes promoted apoptosis and repressed proliferation of HUVECs. Down-regulated/up-regulated 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.
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 PANC-1 cells-derived exosomes promoted apoptosis and repressed proliferation of HUVECs. Down-regulated/up-regulated 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.
Keywords:
Angiogenesis; Exosomes; High mobility group A1; Human microvascular endothelial cells; Long non-coding RNA colon cancer-associated transcript-1; MicroRNA-138-5p; Pancreatic cancer
Authors: Ba Da Yun; Ye Ji Choi; Seung Wan Son; Gabriel Adelman Cipolla; Fernanda Costa Brandão Berti; Danielle Malheiros; Tae-Jin Oh; Hyo Jeong Kuh; Soo Young Choi; Jong Kook Park Journal: Int J Mol Sci Date: 2022-01-15 Impact factor: 5.923