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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Glioblastoma | Primary research

Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1

Authors: Meng Wang, Yi Zhao, Zhi-Yun Yu, Ren-De Zhang, Shu-Ang Li, Peng Zhang, Ti-Kun Shan, Xue-You Liu, Ze-Ming Wang, Pei-Chao Zhao, Hong-Wei Sun

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma.

Methods

Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo.

Results

miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis.

Conclusion

Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.
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Literature
1.
Robert SM, Buckingham SC, Campbell SL, Robel S, Holt KT, Ogunrinu-Babarinde T, Warren PP, White DM, Reid MA, Eschbacher JM, et al. SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Sci Transl Med. 2015;7(289):289ra286.CrossRef
2.
Kundu M, Das S, Dhara D, Mandal M. Prospect of natural products in glioma: a novel avenue in glioma management. Phytother Res. 2019;33(10):2571–84.CrossRefPubMed
3.
He Z, Ruan X, Liu X, Zheng J, Liu Y, Liu L, Ma J, Shao L, Wang D, Shen S, et al. FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma. J Exp Clin Cancer Res. 2019;38(1):65.CrossRefPubMedPubMedCentral
4.
5.
Lang HL, Hu GW, Chen Y, Liu Y, Tu W, Lu YM, Wu L, Xu GH. Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3. Eur Rev Med Pharmacol Sci. 2017;21(5):959–72.PubMed
6.
Zeng AL, Yan W, Liu YW, Wang Z, Hu Q, Nie E, Zhou X, Li R, Wang XF, Jiang T, et al. Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma. Oncogene. 2017;36(38):5369–81.CrossRefPubMedPubMedCentral
7.
Wang ZF, Liao F, Wu H, Dai J. Glioma stem cells-derived exosomal miR-26a promotes angiogenesis of microvessel endothelial cells in glioma. J Exp Clin Cancer Res. 2019;38(1):201.CrossRefPubMedPubMedCentral
8.
Cai Q, Zhu A, Gong L. Exosomes of glioma cells deliver miR-148a to promote proliferation and metastasis of glioblastoma via targeting CADM1. Bull Cancer. 2018;105(7–8):643–51.CrossRefPubMed
9.
Cui D, Sajan P, Shi J, Shen Y, Wang K, Deng X, Zhou L, Hu P, Gao L. MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations. Oncotarget. 2017;8(15):25345–61.CrossRefPubMedPubMedCentral
10.
Wang H, Pan JQ, Luo L, Ning XJ, Ye ZP, Yu Z, Li WS. NF-kappaB induces miR-148a to sustain TGF-beta/Smad signaling activation in glioblastoma. Mol Cancer. 2015;14:2.CrossRefPubMedPubMedCentral
11.
Kunder R, Jalali R, Sridhar E, Moiyadi A, Goel N, Goel A, Gupta T, Krishnatry R, Kannan S, Kurkure P, et al. Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas. Neuro Oncol. 2013;15(12):1644–51.CrossRefPubMedPubMedCentral
12.
Chen X, Yang F, Zhang T, Wang W, Xi W, Li Y, Zhang D, Huo Y, Zhang J, Yang A, et al. MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma. J Exp Clin Cancer Res. 2019;38(1):99.CrossRefPubMedPubMedCentral
13.
Ahn SE, Jeong W, Kim JH, Lim W, Kim J, Bazer FW, Han JY, Song G. ERBB receptor feedback inhibitor 1: identification and regulation by estrogen in chickens. Gen Comp Endocrinol. 2012;175(1):194–205.CrossRefPubMed
14.
Duncan CG, Killela PJ, Payne CA, Lampson B, Chen WC, Liu J, Solomon D, Waldman T, Towers AJ, Gregory SG, et al. Integrated genomic analyses identify ERRFI1 and TACC3 as glioblastoma-targeted genes. Oncotarget. 2010;1(4):265–77.CrossRefPubMedPubMedCentral
15.
Ying H, Zheng H, Scott K, Wiedemeyer R, Yan H, Lim C, Huang J, Dhakal S, Ivanova E, Xiao Y, et al. Mig-6 controls EGFR trafficking and suppresses gliomagenesis. Proc Natl Acad Sci USA. 2010;107(15):6912–7.CrossRefPubMedPubMedCentral
16.
Park E, Kim N, Ficarro SB, Zhang Y, Lee BI, Cho A, Kim K, Park AKJ, Park WY, Murray B, et al. Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6. Nat Struct Mol Biol. 2015;22(9):703–11.CrossRefPubMedPubMedCentral
17.
Cairns J, Fridley BL, Jenkins GD, Zhuang Y, Yu J, Wang L. Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation. EMBO Rep. 2018;19(3):e44767.CrossRefPubMedPubMedCentral
18.
Qu WS, Tian DS, Guo ZB, Fang J, Zhang Q, Yu ZY, Xie MJ, Zhang HQ, Lu JG, Wang W. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury. J Neuroinflammation. 2012;9:178.CrossRefPubMedPubMedCentral
19.
Kim J, Zhang Y, Skalski M, Hayes J, Kefas B, Schiff D, Purow B, Parsons S, Lawler S, Abounader R. microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma. Cancer Res. 2014;74(5):1541–53.CrossRefPubMedPubMedCentral
20.
Shi L, Wang Z, Geng X, Zhang Y, Xue Z. Exosomal miRNA-34 from cancer-associated fibroblasts inhibits growth and invasion of gastric cancer cells in vitro and in vivo. Aging (Albany NY). 2020;12(9):8549–64.CrossRef
21.
Li Y, Li W, Zeng X, Tang X, Zhang S, Zhong F, Peng X, Zhong Y, Rosol TJ, Deng X, et al. The role of microRNA-148a and downstream DLGAP1 on the molecular regulation and tumor progression on human glioblastoma. Oncogene. 2019;38(47):7234–48.CrossRefPubMed
22.
Walsh KM, Codd V, Smirnov IV, Rice T, Decker PA, Hansen HM, Kollmeyer T, Kosel ML, Molinaro AM, McCoy LS, et al. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat Genet. 2014;46(7):731–5.CrossRefPubMedPubMedCentral
23.
Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, et al. Glioma. Nat Rev Dis Primers. 2015;1:15017.CrossRefPubMed
24.
Tan Z, Chen K, Wu W, Zhou Y, Zhu J, Wu G, Cao L, Zhang X, Guan H, Yang Y, et al. Overexpression of HOXC10 promotes angiogenesis in human glioma via interaction with PRMT5 and upregulation of VEGFA expression. Theranostics. 2018;8(18):5143–58.CrossRefPubMedPubMedCentral
25.
Wang XX, Wang Y, Wang PP, Li Y. Expression of MicroRNA-148/152 Family in the Hematological Malignancies. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015;23(4):1173–8.PubMed
26.
Bai M, Li J, Yang H, Zhang H, Zhou Z, Deng T, Zhu K, Ning T, Fan Q, Ying G, et al. miR-135b delivered by gastric tumor exosomes inhibits FOXO1 expression in endothelial cells and promotes angiogenesis. Mol Ther. 2019;27(10):1772–833.CrossRefPubMedPubMedCentral
27.
Ge H, Shrestha A, Liu C, Wu P, Cheng B. MicroRNA 148a–3p promotes thrombospondin-4 expression and enhances angiogenesis during tendinopathy development by inhibiting Kruppel-like factor 6. Biochem Biophys Res Commun. 2018;502(2):276–82.CrossRefPubMed
28.
Spath F, Andersson U, Dahlin AM, Langseth H, Hovig E, Johannesen TB, Grankvist K, Bjorkblom B, Wibom C, Melin B. Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study. Tumour Biol. 2016;37(8):11065–72.CrossRefPubMed
29.
Li B, Liu YH, Sun AG, Huan LC, Li HD, Liu DM. MiR-130b functions as a tumor promoter in glioma via regulation of ERK/MAPK pathway. Eur Rev Med Pharmacol Sci. 2017;21(12):2840–6.PubMed
30.
Yang J, Zhang JN, Chen WL, Wang GS, Mao Q, Li SQ, Xiong WH, Lin YY, Ge JW, Li XX, et al. Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway. Oncotarget. 2017;8(24):38444–55.CrossRefPubMedPubMedCentral
31.
Deng Y, Wang J, Huang M, Xu G, Wei W, Qin H. Inhibition of miR-148a-3p resists hepatocellular carcinoma progress of hepatitis C virus infection through suppressing c-Jun and MAPK pathway. J Cell Mol Med. 2019;23(2):1415–26.CrossRefPubMed
Metadata
Title
Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1
Authors
Meng Wang
Yi Zhao
Zhi-Yun Yu
Ren-De Zhang
Shu-Ang Li
Peng Zhang
Ti-Kun Shan
Xue-You Liu
Ze-Ming Wang
Pei-Chao Zhao
Hong-Wei Sun
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01566-4

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