MicroRNA‑218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2 Corrigendum in /10.3892/or.2022.8406

Mu,Lijun; Guan,Bing; Tian,Juanhua; Li,Xiang; Long,Qingzhi; Wang,Meiyu; Wang,Wen; She,Junjun; Li,Xudong; Wu,Dapeng; Du,Yuefeng

doi:10.3892/or.2020.7759

MicroRNA‑218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2

Corrigendum in: /10.3892/or.2022.8406

Authors:
- Lijun Mu
- Bing Guan
- Juanhua Tian
- Xiang Li
- Qingzhi Long
- Meiyu Wang
- Wen Wang
- Junjun She
- Xudong Li
- Dapeng Wu
- Yuefeng Du
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Affiliations: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Outpatient, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: September 8, 2020 https://doi.org/10.3892/or.2020.7759
Pages: 1961-1970
Copyright: © Mu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA‑218 (miR‑218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR‑218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR‑218 was decreased in RCC tumor tissues and cell lines as detected by real‑time PCR analysis. Tube formation assays and migration assays also confirmed that miR‑218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR‑218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR‑218 targets GRB2‑associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA‑218 may be a therapeutic target for the treatment of RCC.

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1	Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, Heng DY, Larkin J and Ficarra V: Renal cell carcinoma. Nat Rev Dis Primers. 3:170092017. View Article : Google Scholar : PubMed/NCBI
2	Lebacle C, Pooli A, Bessede T, Irani J, Pantuck AJ and Drakaki A: Epidemiology, biology and treatment of sarcomatoid RCC: Current state of the art. World J Urol. 37:115–123. 2019. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
4	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
5	Posadas EM and Figlin RA: Systemic therapy in renal cell carcinoma: Advancing paradigms. Oncology (Williston Park). 26:290–301. 2012.PubMed/NCBI
6	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI
7	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar : PubMed/NCBI
8	Filipowicz W, Bhattacharyya SN and Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 9:102–114. 2008. View Article : Google Scholar : PubMed/NCBI
9	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
10	Liang H, Ge F, Xu Y, Xiao J, Zhou Z, Liu R and Chen C: miR-153 inhibits the migration and the tube formation of endothelial cells by blocking the paracrine of angiopoietin 1 in breast cancer cells. Angiogenesis. 21:849–860. 2018. View Article : Google Scholar : PubMed/NCBI
11	Vosgha H, Ariana A, Smith RA and Lam AK: miR-205 targets angiogenesis and EMT concurrently in anaplastic thyroid carcinoma. Endocr Relat Cancer. 25:323–337. 2018. View Article : Google Scholar : PubMed/NCBI
12	Kinoshita T, Hanazawa T, Nohata N, Kikkawa N, Enokida H, Yoshino H, Yamasaki T, Hidaka H, Nakagawa M, Okamoto Y and Seki N: Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma. Oncotarget. 3:1386–1400. 2012. View Article : Google Scholar : PubMed/NCBI
13	Uesugi A, Kozaki K, Tsuruta T, Furuta M, Morita K, Imoto I, Omura K and Inazawa J: The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer. Cancer Res. 71:5765–5778. 2011. View Article : Google Scholar : PubMed/NCBI
14	Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S, Guo X, Wang B, Gang Y, Zhang Y, et al: MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet. 6:e10008792010. View Article : Google Scholar : PubMed/NCBI
15	Small EM and Olson EN: Pervasive roles of microRNAs in cardiovascular biology. Nature. 469:336–342. 2011. View Article : Google Scholar : PubMed/NCBI
16	Guan B, Wu K, Zeng J, Xu S, Mu L, Gao Y, Wang K, Ma Z, Tian J, Shi Q, et al: Tumor-suppressive microRNA-218 inhibits tumor angiogenesis via targeting the mTOR component RICTOR in prostate cancer. Oncotarget. 8:8162–8172. 2017. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Gao Y, Wu K, Chen Y, Zhou J, Du C, Shi Q, Xu S, Jia J, Tang X, Li F, et al: Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription. Oncotarget. 6:43791–43805. 2015. View Article : Google Scholar : PubMed/NCBI
19	Incoronato M, Urso L, Portela A, Laukkanen MO, Soini Y, Quintavalle C, Keller S, Esteller M and Condorelli G: Epigenetic regulation of miR-212 expression in lung cancer. PLoS One. 6:e277222011. View Article : Google Scholar : PubMed/NCBI
20	Leite KR, Tomiyama A, Reis ST, Sousa-Canavez JM, Sañudo A, Camara-Lopes LH and Srougi M: MicroRNA expression profiles in the progression of prostate cancer-from high-grade prostate intraepithelial neoplasia to metastasis. Urol Oncol. 31:796–801. 2013. View Article : Google Scholar : PubMed/NCBI
21	Grammatikakis I, Gorospe M and Abdelmohsen K: Modulation of cancer traits by tumor suppressor microRNAs. Int J Mol Sci. 14:1822–1842. 2013. View Article : Google Scholar : PubMed/NCBI
22	Venkataraman S, Birks DK, Balakrishnan I, Alimova I, Harris PS, Patel PR, Handler MH, Dubuc A, Taylor MD, Foreman NK and Vibhakar R: MicroRNA 218 acts as a tumor suppressor by targeting multiple cancer phenotype-associated genes in medulloblastoma. J Biol Chem. 288:1918–1928. 2013. View Article : Google Scholar : PubMed/NCBI
23	Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 82:4–6. 1990. View Article : Google Scholar : PubMed/NCBI
24	Karumanchi SA, Merchan J and Sukhatme VP: Renal cancer: Molecular mechanisms and newer therapeutic options. Curr Opin Nephrol Hypertens. 11:37–42. 2002. View Article : Google Scholar : PubMed/NCBI
25	Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1:27–31. 1995. View Article : Google Scholar : PubMed/NCBI
26	Aishima S, Taguchi K, Sugimachi K, Asayama Y, Nishi H, Shimada M, Sugimachi K and Tsuneyoshi M: The role of thymidine phosphorylase and thrombospondin-1 in angiogenesis and progression of intrahepatic cholangiocarcinoma. Int J Surg Pathol. 10:47–56. 2002. View Article : Google Scholar : PubMed/NCBI
27	Ferrara N: VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2:795–803. 2002. View Article : Google Scholar : PubMed/NCBI
28	Jacobsen J, Grankvist K, Rasmuson T, Bergh A, Landberg G and Ljungberg B: Expression of vascular endothelial growth factor protein in human renal cell carcinoma. BJU Int. 93:297–302. 2004. View Article : Google Scholar : PubMed/NCBI
29	Wöhrle FU, Daly RJ and Brummer T: Function, regulation and pathological roles of the Gab/DOS docking proteins. Cell Commun Signal. 7:222009. View Article : Google Scholar : PubMed/NCBI
30	Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K, Gesbert F, Iwasaki H, Li S, Van Etten RA, et al: Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell. 1:479–492. 2002. View Article : Google Scholar : PubMed/NCBI
31	Wang Y, Sheng Q, Spillman MA, Behbakht K and Gu H: Gab2 regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells. Oncogene. 31:2512–2520. 2012. View Article : Google Scholar : PubMed/NCBI
32	Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N, Harris LN, Richardson A, Neel BG and Gu H: A role for the scaffolding adapter GAB2 in breast cancer. Nat Med. 12:114–121. 2006. View Article : Google Scholar : PubMed/NCBI
33	Gu H, Pratt JC, Burakoff SJ and Neel BG: Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation. Mol Cell. 2:729–740. 1998. View Article : Google Scholar : PubMed/NCBI
34	Yang Y, Wu J, Demir A, Castillo-Martin M, Melamed RD, Zhang G, Fukunaga-Kanabis M, Perez-Lorenzo R, Zheng B, Silvers DN, et al: GAB2 induces tumor angiogenesis in NRAS-driven melanoma. Oncogene. 32:3627–3637. 2013. View Article : Google Scholar : PubMed/NCBI