MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression.

Authors

Ling-Zhi Liu, Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Chongyong Li, Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, ChinaFollow
Qi Chen, Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, ChinaFollow
Yi Jing, Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Richard Carpenter, Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Yue Jiang, Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Hsiang-Fu Kung, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Lihui Lai, Institute of Molecular and Chemical Biology, East China Normal University, Shanghai, China
Bing-Hua Jiang, Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

4-1-2011

Comments

This article has been peer reviewed and is published in PLoS One 2010, 5(1). The published version is available at DOI: 10.1371/journal.pone.0019139. © Public Library of Science

Abstract

MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that play important roles in various cellular functions and tumor development. Recent studies have indicated that miR-21 is one of the important miRNAs associated with tumor growth and metastasis, but the role and molecular mechanism of miR-21 in regulating tumor angiogenesis remain to be elucidated. In this study, miR-21 was overexpressed by transfecting pre-miR-21 into human prostate cancer cells and tumor angiogenesis was assayed using chicken chorioallantoic membrane (CAM). We found that overexpression of miR-21 in DU145 cells increased the expression of HIF-1α and VEGF, and induced tumor angiogenesis. AKT and extracellular regulated kinases (ERK) 1/2 are activated by miR-21. Inhibition of miR-21 by the antigomir blocked this process. Overexpression of the miR-21 target, PTEN, also inhibited tumor angiogenesis by partially inactivating AKT and ERK and decreasing the expression of HIF-1 and VEGF. The AKT and ERK inhibitors, LY294002 and U0126, suppressed HIF-1α and VEGF expression and angiogenesis. Moreover, inhibition of HIF-1α expression alone abolished miR-21-inducing tumor angiogenesis, indicating that HIF-1α is required for miR-21-upregulated angiogenesis. Therefore, we demonstrate that miR-21 induces tumor angiogenesis through targeting PTEN, leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing HIF-1α and VEGF expression; HIF-1α is a key downstream target of miR-21 in regulating tumor angiogenesis.

Recommended Citation

Liu, Ling-Zhi; Li, Chongyong; Chen, Qi; Jing, Yi; Carpenter, Richard; Jiang, Yue; Kung, Hsiang-Fu; Lai, Lihui; and Jiang, Bing-Hua, "MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression." (2011). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 69.
https://jdc.jefferson.edu/pacbfp/69

PubMed ID

21544242