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Cancer Cell International
Published in: Cancer Cell International 1/2021

01-12-2021 | Gastric Cancer | Primary research

lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p

Authors: Shuyi Han, Yan Qi, Yihui Xu, Min Wang, Jun Wang, Jing Wang, Mingjie Yuan, Yanfei Jia, Xiaoli Ma, Yunshan Wang, Xiangdong Liu

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

Gastric cancer (GC) remains an important cancer worldwide. Further understanding of the molecular mechanisms of gastric carcinogenesis will enhance the diagnosis and treatment of GC.

Methods

The expression of DLEU2 and ETS2 was analyzed in several GC cell lines using GEPIA online analyze, qRT-PCR and immunohistochemistry. The biological behavior of GC cells was detected by CCK8, clone formation, transwell, wound healing, western blot, and flow cytometry assay. More in-depth mechanisms were studied.

Results

DLEU2 was significantly up-regulated in GC tissues and cell lines. The expression of DLEU2 was significantly associated with pathological grading and TNM stage of GC patients. Furthermore, knockdown of DLEU2 inhibited the proliferation, migration, and invasion of AGS and MKN-45 cells, while overexpression of DLEU2 promoted the proliferation, migration, and invasion of HGC-27 cells. MiR-30a-5p could directly bind to the 3’ UTR region of ETS2. Moreover, DLEU2 bound to miR-30a-5p through the same binding site, which facilitated the expression of ETS2. Knockdown of DLEU2 reduced the protein level of intracellular ETS2 and inhibited AKT phosphorylation, while overexpression of DLEU2 induced the expression of ETS2 and the phosphorylation of AKT. ETS2 was highly expressed in GC tissues. The expression of ETS2 was significantly associated with age, pathological grading, and TNM stage. ETS2 overexpression promoted cell proliferation and migration of AGS and MKN-45 cells. Furthermore, ETS2 overexpression rescued cell proliferation and migration inhibition induced by DLEU2 down-regulation and miR-30a-5p up-regulation in AGS and MKN-45 cells.

Conclusions

DLEU2 is a potential molecular target for GC treatment.
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed
2.
Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363–85.CrossRefPubMed
3.
Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020;396(10251):635–48.CrossRefPubMed
4.
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, et al. Landscape of transcription in human cells. Nature. 2012;489(7414):101–8.CrossRefPubMedPubMedCentral
5.
Furuno M, Pang KC, Ninomiya N, Fukuda S, Frith MC, Bult C, Kai C, Kawai J, Carninci P, Hayashizaki Y, et al. Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLoS Genet. 2006;2(4):e37.CrossRefPubMedPubMedCentral
6.
Zong W, Ju S, Jing R, Cui M. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer. Clin Chem Lab Med. 2018;56(11):1828–37.CrossRefPubMed
7.
Whitehead J, Pandey GK, Kanduri C. Regulation of the mammalian epigenome by long noncoding RNAs. Biochim Biophys Acta. 2009;1790(9):936–47.CrossRefPubMed
8.
Sun TT, He J, Liang Q, Ren LL, Yan TT, Yu TC, Tang JY, Bao YJ, Hu Y, Lin Y, et al. LncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern. Cancer Discov. 2016;6(7):784–801.CrossRefPubMed
9.
Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, Ye G, Zhang X, Xiao B, Guo J. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer. 2014;120(21):3320–8.CrossRefPubMed
10.
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.CrossRefPubMedPubMedCentral
11.
12.
Peng W, Si S, Zhang Q, Li C, Zhao F, Wang F, Yu J, Ma R. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015;34:79.CrossRefPubMedPubMedCentral
13.
Fan ZY, Liu W, Yan C, Zhu ZL, Xu W, Li JF, Su L, Li C, Zhu ZG, Liu B, et al. Identification of a five-lncRNA signature for the diagnosis and prognosis of gastric cancer. Tumour Biol. 2016;37(10):13265–77.CrossRefPubMed
14.
Garding A, Bhattacharya N, Claus R, Ruppel M, Tschuch C, Filarsky K, Idler I, Zucknick M, Caudron-Herger M, Oakes C, et al. Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the In Cis downregulation of a gene cluster that targets NF-kB. PLoS Genet. 2013;9(4):e1003373.CrossRefPubMedPubMedCentral
15.
Migliazza A, Bosch F, Komatsu H, Cayanis E, Martinotti S, Toniato E, Guccione E, Qu X, Chien M, Murty VV. Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia. Blood. 2001;97(7):2098.CrossRefPubMed
16.
17.
Liu Y, Zhu J, Ma X, Han S, Xiao D, Jia Y, Wang Y. ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection. J Cell Physiol. 2019;234(5):7128–40.CrossRefPubMed
18.
Du X, Liu B, Luan X, Cui Q, Li L. miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy. Exp Ther Med. 2018;15(1):599–605.PubMed
19.
Liu X, Ji Q, Zhang C, Liu X, Liu Y, Liu N, Sui H, Zhou L, Wang S, Li Q. miR-30a acts as a tumor suppressor by double-targeting COX-2 and BCL9 in H. pylori gastric cancer models. Sci Rep. 2017;7(1):7113.CrossRefPubMedPubMedCentral
20.
Wei GH, Badis G, Berger MF, Kivioja T, Palin K, Enge M, Bonke M, Jolma A, Varjosalo M, Gehrke AR, et al. Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo. EMBO J. 2010;29(13):2147–60.CrossRefPubMedPubMedCentral
21.
Buggy Y, Maguire TM, McDermott E, Hill AD, O’Higgins N, Duffy MJ. Ets2 transcription factor in normal and neoplastic human breast tissue. Eur J Cancer. 2006;42(4):485–91.CrossRefPubMed
22.
Carbone GM, Napoli S, Valentini A, Cavalli F, Watson DK, Catapano CV. Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells. Nucleic Acids Res. 2004;32(14):4358–67.CrossRefPubMedPubMedCentral
23.
Zhou Y, Shi H, Du Y, Zhao G, Wang X, Li Q, Liu J, Ye L, Shen Z, Guo Y, et al. lncRNA DLEU2 modulates cell proliferation and invasion of non-small cell lung cancer by regulating miR-30c-5p/SOX9 axis. Aging (Albany NY). 2019;11(18):7386–401.CrossRef
24.
Xie Z, Li X, Chen H, Zeng A, Shi Y, Tang Y. The lncRNA-DLEU2/miR-186-5p/PDK3 axis promotes the progress of glioma cells. Am J Transl Res. 2019;11(8):4922–34.PubMedPubMedCentral
25.
Lu T, Wang R, Cai H, Cui Y. Long non-coding RNA DLEU2 promotes the progression of esophageal cancer through miR-30e-5p/E2F7 axis. Biomed Pharmacother. 2020;123:109650.CrossRefPubMed
26.
Ma W, Zhang CQ, Dang CX, Cai HY, Li HL, Miao GY, Wang JK, Zhang LJ. Upregulated long-non-coding RNA DLEU2 exon 9 expression was an independent indicator of unfavorable overall survival in patients with esophageal adenocarcinoma. Biomed Pharmacother. 2019;113:108655.CrossRefPubMed
27.
28.
Guo Y, Bai M, Lin L, Huang J, An Y, Liang L, Liu Y, Huang W. LncRNA DLEU2 aggravates the progression of hepatocellular carcinoma through binding to EZH2. Biomed Pharmacother. 2019;118:109272.CrossRefPubMed
29.
30.
Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339(6119):580–4.CrossRefPubMedPubMedCentral
31.
Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, Uesugi M, Agoulnik S, Taylor N, Funahashi Y, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer. 2014;110(6):1497–505.CrossRefPubMedPubMedCentral
32.
Owczarek CM, Portbury KJ, Hardy MP, O’Leary DA, Kudoh J, Shibuya K, Shimizu N, Kola I, Hertzog PJ. Detailed mapping of the ERG-ETS2 interval of human chromosome 21 and comparison with the region of conserved synteny on mouse chromosome 16. Gene. 2004;324:65–77.CrossRefPubMed
33.
Basuyaux JP, Ferreira E, Stéhelin D, Butticè GJ. The Ets transcription factors interact with each other and with the c-Fos/c-Jun Complex via distinct protein domains in a DNA-dependent and -independent manner. J Biol Chem. 1997;272(42):26188–95.CrossRefPubMed
34.
Heidenreich B, Kumar R. TERT promoter mutations in telomere biology. Mutat Res. 2017;771:15–31.CrossRef
35.
Heidenreich B, Nagore E, Rachakonda PS, Garcia-Casado Z, Requena C, Traves V, Becker J, Soufir N, Hemminki K, Kumar R. Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma. Nat Commun. 2014;5:3401.CrossRefPubMed
36.
Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science. 2015;350(6265):1193–8.CrossRefPubMed
37.
38.
Fontana RJ. Management of patients with decompensated HBV cirrhosis. Semin Liver Dis. 2003;23(1):89–100.CrossRefPubMed
Metadata
Title
lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p
Authors
Shuyi Han
Yan Qi
Yihui Xu
Min Wang
Jun Wang
Jing Wang
Mingjie Yuan
Yanfei Jia
Xiaoli Ma
Yunshan Wang
Xiangdong Liu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02074-9

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