lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis
Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). However, the molecular basis for cancer initiation, development, and progression remains unclear. In this...
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doaj-b784c4d68224438088908fa4044a857a2020-11-25T03:11:52ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-06-0120438450lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT AxisHailu Wu0Ming Wei1Xinglu Jiang2Jiacheng Tan3Wei Xu4Xiaobo Fan5Rui Zhang6Chenbo Ding7Fengfeng Zhao8Xiangyu Shao9Zhigang Zhang10Ruihua Shi11Weijia Zhang12Guoqiu Wu13Medical School of Southeast University, Nanjing 210009, People’s Republic of China; Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaDepartment of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaMedical School of Southeast University, Nanjing 210009, People’s Republic of ChinaDepartment of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaMedical School of Southeast University, Nanjing 210009, People’s Republic of ChinaMedical School of Southeast University, Nanjing 210009, People’s Republic of ChinaMedical School of Southeast University, Nanjing 210009, People’s Republic of ChinaMedical School of Southeast University, Nanjing 210009, People’s Republic of ChinaCenter of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaDepartment of Gastrointestinal Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaMedical School of Southeast University, Nanjing 210009, People’s Republic of China; Department of Gastrointestinal Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaDepartment of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaDepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Corresponding author: Weijia Zhang, PhD, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of China; Corresponding author: Guoqiu Wu, PhD, Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of China.Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). However, the molecular basis for cancer initiation, development, and progression remains unclear. In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. In vitro means of PVT1 loss in a CRC cell line inhibit cell proliferation, migration, and invasion. Furthermore, dual-luciferase reporter and RNA pull-down assays indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p, was suppressed by PVT1 knockdown in CRC cells. Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating vascular endothelial growth factor receptor 1 (VEGFR1). We, therefore, show that PVT1 loss combined with miR-16-5p overexpression reduces tumor volume maximally when propagated within a mouse xenograft model. We conclude that the PVT1-miR-16-5p/VEGFA/VEGFR1/AKT axis directly coordinates the response in CRC pathogenesis and suggest PVT1 as a novel target for potential CRC therapy.http://www.sciencedirect.com/science/article/pii/S2162253120300974PVT1miR-16-5pVEGFAAKTCRC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hailu Wu Ming Wei Xinglu Jiang Jiacheng Tan Wei Xu Xiaobo Fan Rui Zhang Chenbo Ding Fengfeng Zhao Xiangyu Shao Zhigang Zhang Ruihua Shi Weijia Zhang Guoqiu Wu |
spellingShingle |
Hailu Wu Ming Wei Xinglu Jiang Jiacheng Tan Wei Xu Xiaobo Fan Rui Zhang Chenbo Ding Fengfeng Zhao Xiangyu Shao Zhigang Zhang Ruihua Shi Weijia Zhang Guoqiu Wu lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis Molecular Therapy: Nucleic Acids PVT1 miR-16-5p VEGFA AKT CRC |
author_facet |
Hailu Wu Ming Wei Xinglu Jiang Jiacheng Tan Wei Xu Xiaobo Fan Rui Zhang Chenbo Ding Fengfeng Zhao Xiangyu Shao Zhigang Zhang Ruihua Shi Weijia Zhang Guoqiu Wu |
author_sort |
Hailu Wu |
title |
lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis |
title_short |
lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis |
title_full |
lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis |
title_fullStr |
lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis |
title_full_unstemmed |
lncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis |
title_sort |
lncrna pvt1 promotes tumorigenesis of colorectal cancer by stabilizing mir-16-5p and interacting with the vegfa/vegfr1/akt axis |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2020-06-01 |
description |
Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). However, the molecular basis for cancer initiation, development, and progression remains unclear. In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. In vitro means of PVT1 loss in a CRC cell line inhibit cell proliferation, migration, and invasion. Furthermore, dual-luciferase reporter and RNA pull-down assays indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p, was suppressed by PVT1 knockdown in CRC cells. Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating vascular endothelial growth factor receptor 1 (VEGFR1). We, therefore, show that PVT1 loss combined with miR-16-5p overexpression reduces tumor volume maximally when propagated within a mouse xenograft model. We conclude that the PVT1-miR-16-5p/VEGFA/VEGFR1/AKT axis directly coordinates the response in CRC pathogenesis and suggest PVT1 as a novel target for potential CRC therapy. |
topic |
PVT1 miR-16-5p VEGFA AKT CRC |
url |
http://www.sciencedirect.com/science/article/pii/S2162253120300974 |
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