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

Open Access 01-12-2020 | Primary research

LncRNA MSC-AS1 aggravates nasopharyngeal carcinoma progression by targeting miR-524-5p/nuclear receptor subfamily 4 group A member 2 (NR4A2)

Authors: Hongchao Yao, Like Yang, Linli Tian, Yan Guo, Yushan Li

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Nasopharyngeal carcinoma (NPC) is a subtype of head and neck cancer with dismal prognosis and high relapse rate. The role of long non-coding RNAs (lncRNAs) in NPC has become a research hotspot in recent years. This study aimed to interrogate the function and mechanism of lncRNA MSC antisense RNA 1 (MSC-AS1) in NPC.

Methods

MSC-AS1 level in NPC tissues and cells were detected by RT-qPCR. Function of MSC-AS1 in NPC cells was assessed by CCK-8, EdU, TUNEL, caspase-3 activity, and transwell invasion assay. Interaction of microRNA-524-5p (miR-524-5p) with MSC-AS1 and nuclear receptor subfamily 4 group A member 2 (NR4A2) was determined by RIP and luciferase reporter assays.

Results

MSC-AS1 was upregulated in NPC tissues and cells. Functional assays indicated that MSC-AS1 exacerbated cell proliferation, hindered apoptosis, and facilitated invasion and epithelial-to-mesenchymal transition (EMT) in NPC. Mechanistically, MSC-AS1 sequestered miR-524-5p to upregulate NR4A2 expression in NPC cells. Finally, NR4A2 was conformed as an oncogene in NPC, and overexpressed NR4A2 could restore MSC-AS1 knockdown-mediated inhibition on NPC progression.

Conclusions

Our study firstly showed that lncRNA MSC-AS1 aggravated NPC progression by sponging miR-524-5p to increase NR4A2 expression, indicating MSC-AS1 as a novel target for the lncRNA-targeted therapy in NPC.
Appendix
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Literature
1.
Gong Z, Zhang S, Zeng Z, Wu H, Yang Q, Xiong F, Shi L, Yang J, Zhang W, Zhou Y, et al. LOC401317, a p53-regulated long non-coding RNA, inhibits cell proliferation and induces apoptosis in the nasopharyngeal carcinoma cell line HNE2. PLoS ONE. 2014;9(11):e110674.CrossRef
2.
Tan WL, Tan EH, Lim DWT, Ng QS, Tan DSW, Jain A, Ang MK. Advances in systemic treatment for nasopharyngeal carcinoma. Chin Clin Oncol. 2016;5(2):21.CrossRef
3.
Wang Y, Zhang Y, Ma S. Racial differences in nasopharyngeal carcinoma in the United States. Cancer Epidemiol. 2013;37(6):793–802.CrossRef
4.
Lo K-W, Huang DP. Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):451–62.CrossRef
5.
Xing Y-H, Bai Z, Liu C-X, Hu S-B, Ruan M, Chen L-L. Research progress of long noncoding RNA in China. IUBMB Life. 2016;68(11):887–93.CrossRef
6.
Zhang H, Chen Z, Wang X, Huang Z, He Z, Chen Y. Long non-coding RNA: a new player in cancer. J Hematol Oncol. 2013;6:37.CrossRef
7.
Lian Y, Xiong F, Yang L, Bo H, Gong Z, Wang Y, Wei F, Tang Y, Li X, Liao Q, et al. Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway. J Exp Clin Cancer Res. 2018;37(1):253.CrossRef
8.
Wu J, Du M, Zhang Q, Zhang W, Fan Y, Yin L, Fei Q, Jiang X, Chen W, Zhu H, et al. Long noncoding RNA UCA1 promotes the proliferation, invasion, and migration of nasopharyngeal carcinoma cells via modulation of miR-145. OncoTargets Ther. 2018;11:7483–92.CrossRef
9.
Gu J-X, Zhang X, Miao R-C, Xiang X-H, Fu Y-N, Zhang J-Y, Liu C, Qu K. Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma. World J Gastroenterol. 2019;25(2):220–32.CrossRef
10.
Sun Y, Wang P, Yang W, Shan Y, Zhang Q, Wu H. The role of lncRNA MSC-AS1/miR-29b-3p axis-mediated CDK14 modulation in pancreatic cancer proliferation and Gemcitabine-induced apoptosis. Cancer Biol Ther. 2019;20(6):729–39.CrossRef
11.
Zhang N, Hu X, He S, Ding W, Wang F, Zhao Y, Huang Z. LncRNA MSC-AS1 promotes osteogenic differentiation and alleviates osteoporosis through sponging microRNA-140-5p to upregulate BMP2. Biochem Biophys Res Commun. 2019;519(4):790–6.CrossRef
12.
Zheng YJ, Zhao JY, Liang TS, Wang P, Wang J, Yang DK, Liu ZS. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma. FASEB J. 2019;33(11):12915–28.CrossRef
13.
Gao C, Lu W, Lou W, Wang L, Xu Q. Long noncoding RNA HOXC13-AS positively affects cell proliferation and invasion in nasopharyngeal carcinoma via modulating miR-383-3p/HMGA2 axis. J Cell Physiol. 2019;234(8):12809–20.CrossRef
14.
Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466(7308):835–40.CrossRef
15.
Zheng Z, Qu JQ, Yi HM, Ye X, Huang W, Xiao T, Li JY, Wang YY, Feng J, Zhu JF, et al. MiR-125b regulates proliferation and apoptosis of nasopharyngeal carcinoma by targeting A20/NF-κB signaling pathway. Cell Death Dis. 2017;8(6):e2855.CrossRef
16.
Li Y, Zheng F, Xiao X, Xie F, Tao D, Huang C, Liu D, Wang M, Wang L, Zeng F, et al. CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 2017;18(9):1646–59.CrossRef
17.
Liu Y, Tao Z, Qu J, Zhou X, Zhang C. Long non-coding RNA PCAT7 regulates ELF2 signaling through inhibition of miR-134-5p in nasopharyngeal carcinoma. Biochem Biophys Res Commun. 2017;491(2):374–81.CrossRef
18.
Wang L, Ma X, Yan L, Wang T, Wen J, Mi G. LncRNA SNHG1 negatively regulates miR-145a-5p to enhance NUAK1 expression and promote cancer cell metastasis and invasion in nasopharyngeal carcinoma. J Cell Physiol. 2017;234:3119.
19.
Zhen W, Qiu D, Zhiyong C, Xin W, Mengyao J, Dimin Z, Chonghui H, Haijun W, Yonghong Z. MicroRNA-524-5p functions as a tumor suppressor in a human pituitary tumor-derived cell line. Horm Metab Res. 2017;49(07):550–7.CrossRef
20.
Liu G-H, Liu Y-H, Yang Z, Zhu AL, Zhao C-L. MicroRNA-524-5p suppresses the growth and invasive abilities of gastric cancer cells. Oncology Lett. 2016;11(3):1926–32.CrossRef
21.
Liu S-M, Lu J, Lee H-C, Chung F-H, Ma N. miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2. Oncotarget. 2014;5(19):9444–59.PubMedPubMedCentral
22.
Chen L, Zhang W, Yan W, Han L, Zhang K, Shi Z, Zhang J, Wang Y, Li Y, Yu S, et al. The putative tumor suppressor miR-524–5p directly targets jagged-1 and Hes-1 in glioma. Carcinogenesis. 2012;33(11):2276–82.CrossRef
23.
Maxwell MA, Muscat GEO. The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl Recept Signal. 2006;4:e002.CrossRef
24.
Smith AG, Lim W, Pearen M, Muscat GEO, Sturm RA. Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells. Pigment Cell Melanoma Res. 2011;24(3):551–63.CrossRef
25.
Ke N, Claassen G, Yu D-H, Albers A, Fan W, Tan P, Grifman M, Hu X, DeFife K, Nguy V, et al. Nuclear hormone receptor NR4A2 is involved in cell transformation and apoptosis. Cancer Res. 2004;64(22):8208.CrossRef
26.
Inamoto T, Papineni S, Chintharlapalli S, Cho S-D, Safe S, Kamat AM. 1,1-Bis(3′-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth. Mol Cancer Ther. 2008;7(12):3825–33.CrossRef
27.
Inamoto T, Czerniak BA, Dinney CP, Kamat AM. Cytoplasmic mislocalization of the orphan nuclear receptor Nurr1 is a prognostic factor in bladder cancer. Cancer. 2010;116(2):340–6.CrossRef
28.
Zhang T, Wang P, Ren H, Fan J, Wang G. NGFI-b nuclear orphan receptor Nurr1 interacts with p53 and suppresses its transcriptional activity. Mol Cancer Res. 2009;7(8):1408.CrossRef
29.
Sun L, Liu M, Sun G-C, Yang X, Qian Q, Feng S, Mackey LV, Coy DH. Notch signaling activation in cervical cancer cells induces cell growth arrest with the involvement of the nuclear receptor NR4A2. J Cancer. 2016;7(11):1388–95.CrossRef
30.
Wang J, Yang J, Li BB, He ZW. High cytoplasmic expression of the orphan nuclear receptor NR4A2 predicts poor survival in nasopharyngeal carcinoma. Asian Pac J Cancer Prev. 2013;14(5):2805–9.CrossRef
31.
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–102.CrossRef
32.
Li JH, Liu S, Zhou H, Qu LH, Yang JH. decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42((Database issue):):D92–7.CrossRef
33.
Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription? Sci Adv. 2017;3(9):eaao2110.CrossRef
34.
Luo J, Wang K, Yeh S, Sun Y, Liang L, Xiao Y, Xu W, Niu Y, Cheng L, Maity SN, et al. LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling. Nat Commun. 2019;10(1):2571.CrossRef
35.
Wang CJ, Zhu CC, Xu J, Wang M, Zhao WY, Liu Q, Zhao G, Zhang ZZ. Correction to: the lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer. 2019;18(1):129.CrossRef
36.
Chan ATC. Nasopharyngeal carcinoma. Annals Oncol. 2010;21((suppl_7)):vii308–12.CrossRef
37.
Gao W. Chan JY-W, Wong T-S: differential expression of long noncoding RNA in primary and recurrent nasopharyngeal carcinoma. Biomed Res Int. 2014;2014:404567.PubMedPubMedCentral
38.
Shigeishi H, Higashikawa K, Hatano H, Okui G, Tanaka F, Tran TT, Rizqiawan A, Ono S, Tobiume K, Kamata N. PGE2 targets squamous cell carcinoma cell with the activated epidermal growth factor receptor family for survival against 5-fluorouracil through NR4A2 induction. Cancer Lett. 2011;307(2):227–36.CrossRef
39.
Holla VR, Mann JR, Shi Q, DuBois RN. Prostaglandin E2 regulates the nuclear receptor NR4A2 in colorectal cancer. J Biol Chem. 2006;281(5):2676–82.CrossRef
Metadata
Title
LncRNA MSC-AS1 aggravates nasopharyngeal carcinoma progression by targeting miR-524-5p/nuclear receptor subfamily 4 group A member 2 (NR4A2)
Authors
Hongchao Yao
Like Yang
Linli Tian
Yan Guo
Yushan Li
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/s12935-020-01202-1

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