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MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma

  • Authors:
    • Qiong Wang
    • Bin Xu
    • Jixiang Du
    • Xinnv Xu
    • Chao Shang
    • Xiuyu Wang
    • Jinhuan Wang
  • View Affiliations / Copyright

    Affiliations: Tianjin Neurosurgery Institute, Tianjin Key Laboratory of Cerebral Vascular and Neural Degenerative Diseases, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China, The Graduate School, Tianjin Medical University, Tianjin 300060, P.R. China, Department of Critical Care Medicine, Tianjin First Central Hospital, Tianjin 300060, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2139-2149
    |
    Published online on: January 30, 2018
       https://doi.org/10.3892/ijmm.2018.3439
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Abstract

Fms-related tyrosine kinase 1 (Flt1), the receptor of VEGF/PIGF, is associated with cancer angiogenesis and tumorigenesis. Although the high expression of Flt1 in glioma is identified, its regulatory mechanism remains unclear. In the present study, we demonstrate that miR‑139‑5p inhibits Flt1 expression mediated by binding its 3' untranslated region (3'UTR) to regulate the progression of human glioma. We found miR‑139‑5p was downregulated in glioma tissues compared with normal brain tissues whereas a converse expression level of Flt1 was observed. Additionally we proved that miR‑139‑5p directly integrated with the 3'UTR of Flt1 via luciferase activity assay and cells transfected with miR‑139‑5p characterized with a low expression of Flt1 in mRNA and protein levels. Furthermore, we validated that miR‑139‑5p enforced its biological modulation via targeting Flt1 through rescue experiments. miR‑139‑5p suppressed and Flt1 stimulated the malignant activities of glioma cells. We demonstrated that miR‑139‑5p inhibited the Flt1-mediated Wnt/β-catenin signaling pathway in glioma cells. Conclusively, our study indicated that miR‑139‑5p can counteract the malignant phenotypes of glioma cells by the inhibitory effect of the Flt1-mediated Wnt/β-catenin signaling pathway.
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1 

Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al: Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 21:2683–2710. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK and DePinho RA: Malignant glioma: Genetics and biology of a grave matter. Genes Dev. 15:1311–1333. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Takano S, Yamashita T and Ohneda O: Molecular therapeutic targets for glioma angiogenesis. J Oncol. 2010:3519082010. View Article : Google Scholar : PubMed/NCBI

4 

Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Herold-Mende C, Steiner HH, Andl T, Riede D, Buttler A, Reisser C, Fusenig NE and Mueller MM: Expression and functional significance of vascular endothelial growth factor receptors in human tumor cells. Lab Invest. 79:1573–1582. 1999.

6 

Li J, Li L, Li Z, Gong G, Chen P, Liu H, Wang J, Liu Y and Wu X: The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion. Gynecol Oncol. 137:125–133. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Wei SC, Tsao PN, Weng MT, Cao Z and Wong JM: Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway. J Biomed Sci. 20:392013. View Article : Google Scholar : PubMed/NCBI

8 

Fragoso R, Pereira T, Wu Y, Zhu Z, Cabeçadas J and Dias S: VEGFR-1 (FLT-1) activation modulates acute lymphoblastic leukemia localization and survival within the bone marrow, determining the onset of extramedullary disease. Blood. 107:1608–1616. 2006. View Article : Google Scholar

9 

Pierzynski JA, Hildebrandt MA, Kamat AM, Lin J, Ye Y, Dinney CP and Wu X: Genetic variants in the Wnt/β-catenin signaling pathway as indicators of bladder cancer risk. J Urol. 194:1771–1776. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Mir R, Pradhan SJ, Patil P, Mulherkar R and Galande S: Wnt/beta-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression. Oncogene. 35:1679–1691. 2016. View Article : Google Scholar

11 

Wang G, Zhao Y and Zheng Y: MiR-122/Wnt/β-catenin regulatory circuitry sustains glioma progression. Tumour Biol. 35:8565–8572. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Yan Z, Che S, Wang J, Jiao Y, Wang C and Meng Q: miR-155 contributes to the progression of glioma by enhancing Wnt/beta-catenin pathway. Tumour Biol. 36:5323–5331. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Sato F, Tsuchiya S, Meltzer SJ and Shimizu K: MicroRNAs and epigenetics. FEBS J. 278:1598–1609. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Yue S, Wang L, Zhang H, Min Y, Lou Y, Sun H, Jiang Y, Zhang W, Liang A, Guo Y, et al: miR-139-5p suppresses cancer cell migration and invasion through targeting ZEB1 and ZEB2 in GBM. Tumour Biol. 36:6741–6749. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Li RY, Chen LC, Zhang HY, Du WZ, Feng Y, Wang HB, Wen JQ, Liu X, Li XF, Sun Y, et al: miR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma. CNS Neurosci Ther. 19:477–483. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Zhang L, Dong Y, Zhu N, Tsoi H, Zhao Z, Wu CW, Wang K, Zheng S, Ng SS, Chan FK, et al: microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer. Mol Cancer. 13:1242014. View Article : Google Scholar : PubMed/NCBI

18 

Xu W, Hang M, Yuan CY, Wu FL, Chen SB and Xue K: MicroRNA-139-5p inhibits cell proliferation and invasion by targeting insulin-like growth factor 1 receptor in human non-small cell lung cancer. Int J Clin Exp Pathol. 8:3864–3870. 2015.PubMed/NCBI

19 

Wang X, Tong X, Gao H, Yan X, Xu X, Sun S, Wang Q and Wang J: Silencing HIWI suppresses the growth, invasion and migration of glioma cells. Int J Oncol. 45:2385–2392. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Pin AL, Houle F, Fournier P, Guillonneau M, Paquet ÉR, Simard MJ, Royal I and Huot J: Annexin-1-mediated endothelial cell migration and angiogenesis are regulated by vascular endothelial growth factor (VEGF)-induced inhibition of miR-196a expression. J Biol Chem. 287:30541–30551. 2012. View Article : Google Scholar : PubMed/NCBI

21 

El Hallani S, Boisselier B, Peglion F, Rousseau A, Colin C, Idbaih A, Marie Y, Mokhtari K, Thomas JL, Eichmann A, et al: A new alternative mechanism in glioblastoma vascularization: Tubular vasculogenic mimicry. Brain. 133:973–982. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Naik S, Dothager RS, Marasa J, Lewis CL and Piwnica-Worms D: Vascular endothelial growth factor receptor-1 is synthetic lethal to aberrant {beta}-catenin activation in colon cancer. Clin Cancer Res. 15:7529–7537. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Marumoto T and Saya H: Molecular biology of glioma. Adv Exp Med Biol. 746:2–11. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setién F, Casado S, Suarez-Gauthier A, Sanchez-Cespedes M, Git A, et al: Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 67:1424–1429. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Zhang Z, Tang H, Wang Z, Zhang B, Liu W, Lu H, Xiao L, Liu X, Wang R, Li X, et al: miR-185 targets the DNA methyl-transferases 1 and regulates global DNA methylation in human glioma. Mol Cancer. 10:1242011. View Article : Google Scholar

26 

Huang H, Held-Feindt J, Buhl R, Mehdorn HM and Mentlein R: Expression of VEGF and its receptors in different brain tumors. Neurol Res. 27:371–377. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, et al: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 27:740–745. 2009. View Article : Google Scholar :

28 

Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS, et al: Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 31:3212–3218. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Vieira JM, Ruhrberg C and Schwarz Q: VEGF receptor signaling in vertebrate development. Organogenesis. 6:97–106. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Lee TH, Seng S, Sekine M, Hinton C, Fu Y, Avraham HK and Avraham S: Vascular endothelial growth factor mediates intracrine survival in human breast carcinoma cells through internally expressed VEGFR1/FLT1. PLoS Med. 4:e1862007. View Article : Google Scholar : PubMed/NCBI

31 

Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P and Sibilia M: Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell. 140:268–279. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Roybal JD, Zang Y, Ahn YH, Yang Y, Gibbons DL, Baird BN, Alvarez C, Thilaganathan N, Liu DD, Saintigny P, et al: miR-200 inhibits lung adenocarcinoma cell invasion and metastasis by targeting Flt1/VEGFR1. Mol Cancer Res. 9:25–35. 2011. View Article : Google Scholar :

33 

Wang F, Yamauchi M, Muramatsu M, Osawa T, Tsuchida R and Shibuya M: RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. J Biol Chem. 286:9097–9106. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Takahashi M, Matsui A, Inao M, Mochida S and Fujiwara K: ERK/MAPK-dependent PI3K/Akt phosphorylation through VEGFR-1 after VEGF stimulation in activated hepatic stellate cells. Hepatol Res. 26:232–236. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Arqués O, Chicote I, Puig I, Tenbaum SP, Argilés G, Dienstmann R, Fernández N, Caratù G, Matito J, Silberschmidt D, et al: Tankyrase inhibition blocks Wnt/beta-catenin pathway and reverts resistance to PI3K and AKT inhibitors in the treatment of colorectal cancer. Clin Cancer Res. 22:644–656. 2016. View Article : Google Scholar

36 

Zeitlin BD, Ellis LM and Nor JE: Inhibition of vascular endothelial growth factor receptor-1/Wnt/{beta}-catenin crosstalk leads to tumor cell death. Clin Cancer Res. 15:7453–7455. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang Q, Xu B, Du J, Xu X, Shang C, Wang X and Wang J: MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma. Int J Mol Med 41: 2139-2149, 2018.
APA
Wang, Q., Xu, B., Du, J., Xu, X., Shang, C., Wang, X., & Wang, J. (2018). MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma. International Journal of Molecular Medicine, 41, 2139-2149. https://doi.org/10.3892/ijmm.2018.3439
MLA
Wang, Q., Xu, B., Du, J., Xu, X., Shang, C., Wang, X., Wang, J."MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma". International Journal of Molecular Medicine 41.4 (2018): 2139-2149.
Chicago
Wang, Q., Xu, B., Du, J., Xu, X., Shang, C., Wang, X., Wang, J."MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma". International Journal of Molecular Medicine 41, no. 4 (2018): 2139-2149. https://doi.org/10.3892/ijmm.2018.3439
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Q, Xu B, Du J, Xu X, Shang C, Wang X and Wang J: MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma. Int J Mol Med 41: 2139-2149, 2018.
APA
Wang, Q., Xu, B., Du, J., Xu, X., Shang, C., Wang, X., & Wang, J. (2018). MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma. International Journal of Molecular Medicine, 41, 2139-2149. https://doi.org/10.3892/ijmm.2018.3439
MLA
Wang, Q., Xu, B., Du, J., Xu, X., Shang, C., Wang, X., Wang, J."MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma". International Journal of Molecular Medicine 41.4 (2018): 2139-2149.
Chicago
Wang, Q., Xu, B., Du, J., Xu, X., Shang, C., Wang, X., Wang, J."MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma". International Journal of Molecular Medicine 41, no. 4 (2018): 2139-2149. https://doi.org/10.3892/ijmm.2018.3439
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