The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
MiR-21 Induced Angiogenesis through AKT and ERK Activation and HIF-1α Expression
Open accessAbstract
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.
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Cited by
Emami Nejad, A., Najafgholian, S., Rostami, A., Sistani, A., Shojaeifar, S., Esparvarinha, M., Nedaeinia, R., Haghjooy Javanmard, S., Taherian, M., Ahmadlou, M., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-020-01719-5 · Cited by 693
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Hypoxia-regulated microRNAs in human cancer
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Metadata
- Authors
- Liu, L.-Z., Li, C., Chen, Q., Jing, Y., Carpenter, R., Jiang, Y., Kung, H.-F., Lai, L., & Jiang, B.-H.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-04-22
- Volume
- 6
- Issue
- 4
- Pages
- e19139
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2134975640
- Cited by
- 493
- References
- 52
- FWCI
- 10.89
- Type
- journal article
- Language
- en
- Open access
- gold
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