Abstract
Osteosarcoma is one of the most common malignant bone tumors in human worldwide. Angiogenesis is a pivotal process during osteosarcoma development. Insulin-like growth factor 1 (IGF1) has been reported to promote angiogenesis. However, the role of 3′ untranslational region (3′UTR) of IGF1 mRNA in angiogenic activity in osteosarcomas is still unknown. In the present study, we performed gain-of-function assays to investigate the role of IGF1-3′UTR in angiogenesis. For the first time, we demonstrated that IGF1 3′UTR increased VEGF expression and promotes angiogenesis in osteosarcoma cells. In addition, RNA-immunoprecipitation and luciferase reporter assays showed that IGF1 3′UTR was a direct target of miR-29s. Our data also demonstrated that there existed a competition of miR-29s between IGF1-3′UTR and VEGF mRNA, and IGF1-3′UTR promoted angiogenesis at least in part via sponging miR-29s. Taken together, our study suggests that IGF1-3′UTR functions as a ceRNA in promoting angiogenesis by sponging miR-29s in osteosarcoma.
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05 January 2023
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s10735-023-10111-2
References
Bach LA (2015) Endothelial cells and the IGF system. J Mol Endocrinol 54:R1–R13. doi:10.1530/JME-14-0215
Binet F, Sapieha P (2015) ER stress and angiogenesis. Cell Metab. doi:10.1016/j.cmet.2015.07.010
Chen P et al (2012) The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis. J Mol Histol 43:63–70. doi:10.1007/s10735-011-9370-2
Cortez MA et al (2010) miR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma. Genes Chromosom Cancer 49:981–990. doi:10.1002/gcc.20808
Dobrucki LW et al (2010) Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging. J Mol Cell Cardiol 48:1071–1079. doi:10.1016/j.yjmcc.2009.10.008
Fan YC, Mei PJ, Chen C, Miao FA, Zhang H, Li ZL (2013) MiR-29c inhibits glioma cell proliferation, migration, invasion and angiogenesis. J Neurooncol 115:179–188. doi:10.1007/s11060-013-1223-2
Hou CH, Lin FL, Tong KB, Hou SM, Liu JF (2014) Transforming growth factor alpha promotes osteosarcoma metastasis by ICAM-1 and PI3 K/Akt signaling pathway. Biochem Pharmacol 89:453–463. doi:10.1016/j.bcp.2014.03.010
Hu Y et al (2015) Evaluation of miR-29c inhibits endotheliocyte migration and angiogenesis of human endothelial cells by suppressing the insulin like growth factor 1. Am J Transl Res 7:866–877
Isakoff MS, Bielack SS, Meltzer P, Gorlick R (2015) Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. doi:10.1200/JCO.2014.59.4895
Jiang H, Zhang G, Wu JH, Jiang CP (2014) Diverse roles of miR-29 in cancer (review). Oncol Rep 31:1509–1516. doi:10.3892/or.2014.3036
Karginov FV, Hannon GJ (2013) Remodeling of Ago2-mRNA interactions upon cellular stress reflects miRNA complementarity and correlates with altered translation rates. Genes Dev 27:1624–1632. doi:10.1101/gad.215939.113
Liu K, Ying Z, Qi X, Shi Y, Tang Q (2015) MicroRNA-1 regulates the proliferation of vascular smooth muscle cells by targeting insulin-like growth factor 1. Int J Mol Med 36:817–824. doi:10.3892/ijmm.2015.2277
Poliseno L, Pandolfi PP (2015) PTEN ceRNA networks in human cancer. Methods 77–78:41–50. doi:10.1016/j.ymeth.2015.01.013
Qu J, Lu D, Guo H, Miao W, Wu G, Zhou M (2015) MicroRNA-9 regulates osteoblast differentiation and angiogenesis via the AMPK signaling pathway. Mol Cell Biochem. doi:10.1007/s11010-015-2565-1
Rao N, Lee YF, Ge R (2015) Novel endogenous angiogenesis inhibitors and their therapeutic potential. Acta Pharmacol Sin. doi:10.1038/aps.2015.73
Rivas-Fuentes S, Salgado-Aguayo A, Pertuz Belloso S, Gorocica Rosete P, Alvarado-Vasquez N, Aquino-Jarquin G (2015) Role of chemokines in non-small cell lung cancer: angiogenesis and inflammation. J Cancer 6:938–952. doi:10.7150/jca.12286
Shi X, Teng F (2015) Down-regulated miR-28-5p in human hepatocellular carcinoma correlated with tumor proliferation and migration by targeting insulin-like growth factor-1 (IGF-1). Mol Cell Biochem. doi:10.1007/s11010-015-2506-z
Shi SJ, Wang LJ, Yu B, Li YH, Jin Y, Bai XZ (2015) LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget 6:11652–11663
Shigematsu S, Yamauchi K, Nakajima K, Iijima S, Aizawa T, Hashizume K (1999) IGF-1 regulates migration and angiogenesis of human endothelial cells. Endocr J 46(Suppl):S59–S62
Sohi G, Revesz A, Ramkumar J, Hardy DB (2015) Higher hepatic miR-29 expression in undernourished male rats during the postnatal period targets the long-term repression of IGF-1. Endocrinology 156:3069–3076. doi:10.1210/EN.2015-1058
Solarek W, Czarnecka AM, Escudier B, Bielecka ZF, Lian F, Szczylik C (2015) Insulin and IGFs in renal cancer risk and progression. Endocr Relat Cancer 22:R253–R264. doi:10.1530/ERC-15-0135
Tabatabaei SH, Jahanshahi G, Dehghan Marvasti F (2015) Diagnostic challenges of low-grade central osteosarcoma of jaw: a literature review. J Dent 16:62–67
Tang HB, Ren YP, Zhang J, Ma SH, Gao F, Wu YP (2007) Correlation of insulin-like growth factor-1 (IGF-1) to angiogenesis of breast cancer in IGF-1-deficient mice. Ai zheng = Aizheng = Chin J Cancer 26:1215–1220
Toffanin S, Sia D, Villanueva A (2012) microRNAs: new ways to block tumor angiogenesis? J Hepatol 57:490–491. doi:10.1016/j.jhep.2012.06.005
Wang W, Zhang E, Lin C (2015) MicroRNAs in tumor angiogenesis. Life Sci 136:28–35. doi:10.1016/j.lfs.2015.06.025
Xu J et al (2015) The mRNA related ceRNA-ceRNA landscape and significance across 20 major cancer types. Nucleic Acids Res. doi:10.1093/nar/gkv853
Yanaihara N et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198. doi:10.1016/j.ccr.2006.01.025
Yancopoulos GD (2010) Clinical application of therapies targeting VEGF. Cell 143:13–16. doi:10.1016/j.cell.2010.09.028
Yang J et al (2014) FOXO1 3′UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett 588:3218–3224. doi:10.1016/j.febslet.2014.07.003
Zheng L, Li X, Gu Y, Lv X, Xi T (2015) The 3′UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1. Breast Cancer Res Treat 150:105–118. doi:10.1007/s10549-015-3298-2
Zou Y et al (2015) miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients. Carcinogenesis 36:676–684. doi:10.1093/carcin/bgv027
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Gao, S., Cheng, C., Chen, H. et al. RETRACTED ARTICLE: IGF1 3′UTR functions as a ceRNA in promoting angiogenesis by sponging miR-29 family in osteosarcoma. J Mol Histol 47, 135–143 (2016). https://doi.org/10.1007/s10735-016-9659-2
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DOI: https://doi.org/10.1007/s10735-016-9659-2