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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Neuroblastoma | Primary research

Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway

Authors: Huan-yu Zhang, Mao-qing Xing, Jing Guo, Jin-chuan Zhao, Xin Chen, Zhong Jiang, Hong Zhang, Qian Dong

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved.

Methods

Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo.

Results

We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence.

Conclusion

Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.
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Literature
1.
Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003;3:203–16.CrossRef
2.
Ackermann S, Cartolano M, Hero B, Welte A, Kahlert Y, Roderwieser A, Bartenhagen C, Walter E, Gecht J, Kerschke L, et al. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018;362(6419):1165–70.CrossRef
3.
Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74.CrossRef
4.
Marchese FP, Raimondi I, Huarte M. The multidimensional mechanisms of long noncoding RNA function. Genome Biol. 2017;18(1):206.CrossRef
5.
Li D, Wang X, Mei H, Fang E, Ye L, Song H, Yang F, Li H, Huang K, Zheng L, et al. Long noncoding RNA pancEts-1 promotes neuroblastoma progression through hnRNPK-mediated β-catenin stabilization. Cancer Res. 2018;78(5):1169–83.CrossRef
6.
Pandey GK, Mitra S, Subhash S, Hertwig F, Kanduri M, Mishra K, Fransson S, Ganeshram A, Mondal T, Bandaru S. The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. Cancer Cell. 2014;26(5):722–37.CrossRef
7.
Stallings RL. MicroRNA involvement in the pathogenesis of neuroblastoma: potential for microRNA mediated therapeutics. Curr Pharm Des. 2009;15(4):456–62.CrossRef
8.
Liu X, Peng H, Liao W, Luo A, Cai M, He J, Zhang X, Luo Z, Jiang H, Xu L. MiR-181a/b induce the growth, invasion, and metastasis of neuroblastoma cells through targeting ABI1. Mol Carcinog. 2018;57(9):1237–50.CrossRef
9.
Zhang H, Pu J, Qi T, Qi M, Yang C, Li S, Huang K, Zheng L, Tong Q. MicroRNA-145 inhibits the growth, invasion, metastasis and angiogenesis of neuroblastoma cells through targeting hypoxia-inducible factor 2 alpha. Oncogene. 2014;33(3):387–97.CrossRef
10.
Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J, Su H, Tang YL, Kim IM. Crosstalk between long noncoding RNAs and MicroRNAs in health and disease. Int J Mol Sci. 2016;17(3):356.CrossRef
11.
Sun Z, Guo X, Zang M, Wang P, Xue S, Chen G. Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis. J Cell Physiol. 2019;234(2):1336–45.CrossRef
12.
Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature. 2012;483(7391):589–93.CrossRef
13.
Zhao X, Li D, Pu J, Mei H, Yang D, Xiang X, Qu H, Huang K, Zheng L, Tong Q. CTCF cooperates with noncoding RNA MYCNOS to promote neuroblastoma progression through facilitating MYCN expression. Oncogene. 2016;35(27):3565–76.CrossRef
14.
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.CrossRef
15.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.CrossRef
16.
Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;71(1):3–7.CrossRef
17.
Yoon JH, Abdelmohsen K, Gorospe M. Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol. 2014;34:9–14.CrossRef
18.
Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505(7483):344–52.CrossRef
19.
Li H, Guo X, Li Q, Ran P, Xiang X, Yuan Y, Dong T, Zhu B, Wang L, Li F, et al. Long non-coding RNA 1308 promotes cell invasion by regulating the miR-124/ADAM 15 axis in non-small-cell lung cancer cells. Cancer Manag Res. 2018;10:6599–609.CrossRef
20.
An Y, Chen XM, Yang Y, Mo F, Jiang Y, Sun DL, Cai HH. LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer. Cancer Cell Int. 2018;18:143.CrossRef
21.
Datta J, Smith A, Lang JC, Islam M, Dutt D, Teknos TN, Pan Q. microRNA-107 functions as a candidate tumor-suppressor gene in head and neck squamous cell carcinoma by downregulation of protein kinase Cɛ. Oncogene. 2012;31(36):4045–53.CrossRef
22.
Imamura T, Komatsu S, Ichikawa D, Miyamae M, Okajima W, Ohashi T, Kiuchi J, Nishibeppu K, Konishi H, Shiozaki A. Depleted tumor suppressor miR-107 in plasma relates to tumor progression and is a novel therapeutic target in pancreatic cancer. Sci Rep. 2017;7(1):5708.CrossRef
23.
Chen PS, Su JL, Cha ST, Tarn WY, Wang MY, Hsu HC, Lin MT, Chu CY, Hua KT, Chen CN. miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans. J Clin Investig. 2011;121(9):3442–55.CrossRef
24.
Nakagawara A, Azar CG, Scavarda NJ, Brodeu GM. Expression and function of TRK-B and BDNF in human neuroblastomas. Mol Cell Biol. 1994;14(1):759–67.CrossRef
25.
Matsumoto K, Wada RK, Yamashiro JM, Kaplan DR, Thiele CJ. Expression of brain-derived neurotrophic factor and p145TrkB affects survival, differentiation, and invasiveness of human neuroblastoma cells. Cancer Res. 1995;55(8):1798–806.PubMed
26.
Feng X, Jiang H, Baik JC, Edgar C, Eide FF. BDNF dependence in neuroblastoma. J Neurosci Res. 2001;64(4):355–63.CrossRef
27.
Scala S, Wosikowski K, Giannakakou P, Valle P, Biedler JL, Spengler BA, Lucarelli E, Bates SE, Thiele CJ. Brain-derived neurotrophic factor protects neuroblastoma cells from vinblastine toxicity. Cancer Res. 1996;56(16):3737–42.PubMed
Metadata
Title
Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway
Authors
Huan-yu Zhang
Mao-qing Xing
Jing Guo
Jin-chuan Zhao
Xin Chen
Zhong Jiang
Hong Zhang
Qian Dong
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0968-x

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