Long non-coding RNA GATA6-AS1 upregulates GATA6 to regulate the biological behaviors of lung adenocarcinoma cells.
A549 Cells
Adenocarcinoma of Lung
/ genetics
Apoptosis
Biomarkers, Tumor
Cell Line, Tumor
Cell Movement
Cell Proliferation
Disease Progression
Female
GATA6 Transcription Factor
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ genetics
Male
MicroRNAs
/ genetics
Middle Aged
Neoplasm Invasiveness
RNA, Long Noncoding
/ genetics
Up-Regulation
GATA6
GATA6-AS1
Lung adenocarcinoma
MiR-4530
Journal
BMC pulmonary medicine
ISSN: 1471-2466
Titre abrégé: BMC Pulm Med
Pays: England
ID NLM: 100968563
Informations de publication
Date de publication:
15 May 2021
15 May 2021
Historique:
received:
17
02
2021
accepted:
29
04
2021
entrez:
16
5
2021
pubmed:
17
5
2021
medline:
16
11
2021
Statut:
epublish
Résumé
Lung adenocarcinoma (LUAD) is known to be one of the leading causes of cancer-related deaths globally. In recent decades, long non-coding RNAs (lncRNAs) have been indicated to exert pivotal regulating functions in multiple biological behaviors in the initiation and development of LUAD. However, the functional mechanism of lncRNA GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in LUAD has not been explored. In the current study, GATA6-AS1 expression in LUAD tissues was revealed. Meanwhile, GATA6-AS1 expression in LUAD cells was investigated via RT-qPCR analysis. After A549 and H1975 cells were transfected with GATA6-AS1 overexpression plasmids, EdU and colony formation assays, TUNEL assays and flow cytometry analyses, as well as wound healing and Transwell assays were conducted to detect cell proliferation, apoptosis, migration and invasion. Afterwards, bioinformatic tools, western blot analyses, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays were performed to investigate the correlation of microRNA-4530 (miR-4530), GATA6-AS1 and GATA6. We found that GATA6-AS1 expression was low-expressed in LUAD tissues and cells. Furthermore, the upregulation of GATA6-AS1 suppressed the proliferative, migration and invasion abilities, as well as promoted apoptotic rate of A549 and H1975 cells. Moreover, the mechanistic investigations revealed that GATA6-AS1 upregulated the expression of its cognate sense gene GATA6 by binding with miR-4530, thereby modulating the malignant progression of LUAD cells. GATA6-AS1 repressed LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via regulation of the miR-4530/GATA6 axis, indicating GATA6-AS1 as a new prognostic biomarker for LUAD.
Sections du résumé
BACKGROUND
BACKGROUND
Lung adenocarcinoma (LUAD) is known to be one of the leading causes of cancer-related deaths globally. In recent decades, long non-coding RNAs (lncRNAs) have been indicated to exert pivotal regulating functions in multiple biological behaviors in the initiation and development of LUAD. However, the functional mechanism of lncRNA GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in LUAD has not been explored.
METHODS
METHODS
In the current study, GATA6-AS1 expression in LUAD tissues was revealed. Meanwhile, GATA6-AS1 expression in LUAD cells was investigated via RT-qPCR analysis. After A549 and H1975 cells were transfected with GATA6-AS1 overexpression plasmids, EdU and colony formation assays, TUNEL assays and flow cytometry analyses, as well as wound healing and Transwell assays were conducted to detect cell proliferation, apoptosis, migration and invasion. Afterwards, bioinformatic tools, western blot analyses, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays were performed to investigate the correlation of microRNA-4530 (miR-4530), GATA6-AS1 and GATA6.
RESULTS
RESULTS
We found that GATA6-AS1 expression was low-expressed in LUAD tissues and cells. Furthermore, the upregulation of GATA6-AS1 suppressed the proliferative, migration and invasion abilities, as well as promoted apoptotic rate of A549 and H1975 cells. Moreover, the mechanistic investigations revealed that GATA6-AS1 upregulated the expression of its cognate sense gene GATA6 by binding with miR-4530, thereby modulating the malignant progression of LUAD cells.
CONCLUSIONS
CONCLUSIONS
GATA6-AS1 repressed LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via regulation of the miR-4530/GATA6 axis, indicating GATA6-AS1 as a new prognostic biomarker for LUAD.
Identifiants
pubmed: 33992085
doi: 10.1186/s12890-021-01521-7
pii: 10.1186/s12890-021-01521-7
pmc: PMC8126172
doi:
Substances chimiques
Biomarkers, Tumor
0
GATA6 Transcription Factor
0
GATA6 protein, human
0
MIRN4530 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Pagination
166Commentaires et corrections
Type : RetractionIn
Références
Siegel R, Miller K, Jemal AJ. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.
pubmed: 31912902
doi: 10.3322/caac.21590
Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.
pubmed: 21252716
pmcid: 4513953
doi: 10.1097/JTO.0b013e318206a221
Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.
pubmed: 26808342
doi: 10.3322/caac.21338
Altorki N, Markowitz G, Gao D, Port J, Saxena A, Stiles B, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019;19(1):9–31.
pubmed: 30532012
pmcid: 6749995
doi: 10.1038/s41568-018-0081-9
Wood S, Pernemalm M, Crosbie P, Whetton AJC. Molecular histology of lung cancer: from targets to treatments. Cancer Treat Rev. 2015;41(4):361–75.
pubmed: 25825324
doi: 10.1016/j.ctrv.2015.02.008
Landi L, Cappuzzo F. Management of NSCLC: focus on crizotinib. Expert Opin Pharmacother. 2014;15(17):2587–97.
pubmed: 25301075
doi: 10.1517/14656566.2014.970174
Kopp F, Mendell JJC. Functional classification and experimental dissection of long noncoding RNAs. Cell. 2018;172(3):393–407.
pubmed: 29373828
pmcid: 5978744
doi: 10.1016/j.cell.2018.01.011
Lin C, Yang LJ. Long noncoding RNA in cancer: wiring signaling circuitry. Trends Cell Biol. 2018;28(4):287–301.
pubmed: 29274663
doi: 10.1016/j.tcb.2017.11.008
Xu X, Yuan X, Ni J, Guo J, Gao Y, Yin W, et al. MAGI2-AS3 inhibits breast cancer by downregulating DNA methylation of MAGI2. J Cell Physiol. 2020;236:1116–30.
pubmed: 32730644
doi: 10.1002/jcp.29922
Liang Y, Zhang D, Zheng T, Yang G, Wang J, Meng F, et al. lncRNA-SOX2OT promotes hepatocellular carcinoma invasion and metastasis through miR-122-5p-mediated activation of PKM2. Oncogensesis. 2020;9(5):54.
doi: 10.1038/s41389-020-0242-z
Du J, Liang Y, Zhao J, Lin X, Wang ZJ. LINC00858 knockdown inhibits gastric cancer cell growth and induces apoptosis through reducing WNK2 promoter methylation. Cell Oncol (Dordr). 2020;43(4):709–23.
doi: 10.1007/s13402-020-00518-4
Gao W, Guo H, Niu M, Zheng X, Zhang Y, Xue X, et al. circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway. Mol Cancer. 2020;19(1):166.
pubmed: 33234130
pmcid: 7686732
doi: 10.1186/s12943-020-01279-2
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl TJS. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853–8.
pubmed: 11679670
doi: 10.1126/science.1064921
Bartel DJC. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.
pubmed: 14744438
doi: 10.1016/S0092-8674(04)00045-5
Zhang T, Jing L, Li H, Ding L, Ai D, Lyu J, et al. MicroRNA-4530 promotes angiogenesis by targeting VASH1 in breast carcinoma cells. Oncol Lett. 2017;14(1):111–8.
pubmed: 28693142
pmcid: 5494889
doi: 10.3892/ol.2017.6102
Tay Y, Rinn J, Pandolfi PJN. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505(7483):344–52.
pubmed: 24429633
pmcid: 4113481
doi: 10.1038/nature12986
Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8.
pubmed: 21802130
pmcid: 3235919
doi: 10.1016/j.cell.2011.07.014
Wu Q, Guo L, Jiang F, Li L, Chen FJ, et al. Analysis of the miRNA-mRNA-lncRNA networks in ER+ and ER- breast cancer cell lines. J Cell Mol Med. 2015;19(12):2874–87.
pubmed: 26416600
pmcid: 4687702
doi: 10.1111/jcmm.12681
Luo L, Wang M, Li X, Luo C, Tan S, Yin S, et al. A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression. Cancer Cell Int. 2020;20:372.
pubmed: 32774166
pmcid: 7409411
doi: 10.1186/s12935-020-01471-w
Cao Z, Pan X, Yang Y, Huang Y, Shen HJB. The lncLocator: a subcellular localization predictor for long non-coding RNAs based on a stacked ensemble classifier. Bioinformatics. 2018;34(13):2185–94.
pubmed: 29462250
doi: 10.1093/bioinformatics/bty085
Chen Y, Wang XJ. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48:D127–31.
pubmed: 31504780
doi: 10.1093/nar/gkz757
Chang T, Huang H, Hsu J, Weng S, Horng J, Huang HJBB. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinformatics. 2013;14(Suppl 2):S4.
pubmed: 23514235
pmcid: 3599089
doi: 10.1186/1471-2105-14-S2-S4
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.
pubmed: 11846609
doi: 10.1006/meth.2001.1262
Qian W, Cai X, Qian Q, Peng W, Yu J, Zhang X, et al. lncRNA ZEB1-AS1 promotes pulmonary fibrosis through ZEB1-mediated epithelial-mesenchymal transition by competitively binding miR-141-3p. Cell Death Dis. 2019;10(2):129.
pubmed: 30755599
pmcid: 6372615
doi: 10.1038/s41419-019-1339-1
Jiao M, Guo H, Chen Y, Li L, Zhang L. DARS-AS1 promotes clear cell renal cell carcinoma by sequestering miR-194-5p to up-regulate DARS. Biomed Pharmacother. 2020;128:110323.
pubmed: 32526457
doi: 10.1016/j.biopha.2020.110323
Yang T, Chen WC, Shi PC, Liu MR, Jiang T, Song H, et al. Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge. J Exp Clin Cancer Res. 2020;39(1):139.
pubmed: 32690100
pmcid: 7370515
doi: 10.1186/s13046-020-01633-8
Sui Y, Lin G, Zheng Y, Huang W. LncRNA MAFG-AS1 boosts the proliferation of lung adenocarcinoma cells via regulating miR-744-5p/MAFG axis. Eur J Pharmacol. 2019;859:172465.
pubmed: 31211984
doi: 10.1016/j.ejphar.2019.172465
Wilkerson M, Yin X, Walter V, Zhao N, Cabanski C, Hayward M, et al. Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation. PLoS ONE. 2012;7(5):e36530.
pubmed: 22590557
pmcid: 3349715
doi: 10.1371/journal.pone.0036530
Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543–50.
doi: 10.1038/nature13385
Lin S, Sun J, Wu J, Long H, Zhu C, Xiang T, et al. Aberrant microRNAs expression in CD133
pubmed: 22349807
pmcid: 3887701
doi: 10.1007/s10059-012-2252-y
Yang J, Lin J, Liu T, Chen T, Pan S, Huang W, et al. Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. Lung Cancer. 2014;85(2):110–5.
pubmed: 24906504
doi: 10.1016/j.lungcan.2014.05.011
Chen T, Gao F, Yang T, Li H, Li Y, Ren H, et al. LncRNA HOTAIRM1 Inhibits the Proliferation and Invasion of Lung Adenocarcinoma Cells via the miR-498/WWOX Axis. Cancer Manag Res. 2020;12:4379–90.
pubmed: 32606933
pmcid: 7295110
doi: 10.2147/CMAR.S244573
Zheng X, Zhang J, Fang T, Wang X, Wang S, Ma Z, et al. The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway. Oncogenesis. 2020;9(3):34.
pubmed: 32165621
pmcid: 7067885
doi: 10.1038/s41389-020-0217-0
Wang L, Zhang X, Liu Y, Xu SJ. Long noncoding RNA FBXL19-AS1 induces tumor growth and metastasis by sponging miR-203a-3p in lung adenocarcinoma. J Cell Physiol. 2020;235(4):3612–25.
pubmed: 31566718
doi: 10.1002/jcp.29251
Chen W, Tang R, He R, Li D, Liang L, Zeng J, et al. Clinical roles of the aberrantly expressed lncRNAs in lung squamous cell carcinoma: a study based on RNA-sequencing and microarray data mining. Oncotarget. 2017;8(37):61282–304.
pubmed: 28977863
pmcid: 5617423
doi: 10.18632/oncotarget.18058
Gong Z, Chen X, Zhang Y, Liu C, Wang Z, Xu X, et al. LncRNA GATA6-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer via Repressing microRNA-543 to Up-Regulating RKIP. Cancer Manag Res. 2020;12:9327–38.
pubmed: 33061622
pmcid: 7532887
doi: 10.2147/CMAR.S254184
Wang Z, Pan L, Yang L, Lv P, Mai S, Wang Y. Long non-coding RNA GATA6-AS1 sponges miR-324-5p to inhibit lung cancer cell proliferation and invasion. Onco Targets Ther. 2020;13:9741–51.
pubmed: 33061453
pmcid: 7533243
doi: 10.2147/OTT.S256336
Xiong Y, Zhang X, Lin Z, Xiong A, Xie S, Liang J, et al. SFTA1P, LINC00968, GATA6-AS1, TBX5-AS1, and FEZF1-AS1 are crucial long non-coding RNAs associated with the prognosis of lung squamous cell carcinoma. Oncology Lett. 2019;18(4):3985–93.
Guil S, Esteller M. Cis-acting noncoding RNAs: friends and foes. Nat Struct Mol Biol. 2012;19(11):1068–75.
pubmed: 23132386
doi: 10.1038/nsmb.2428
Liu Z, Dai J, Shen HB. Systematic analysis reveals long noncoding RNAs regulating neighboring transcription factors in human cancers. Biochim Biophys Acta Mol Basis Dis. 2018;1864:2785–92.
pubmed: 29753811
doi: 10.1016/j.bbadis.2018.05.006
Huang X, Xiao S, Zhu X, Yu Y, Cao M, Zhang X, et al. miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling. Cell Death Dis. 2020;11(9):785.
pubmed: 32963220
pmcid: 7508872
doi: 10.1038/s41419-020-02997-7
Liang G, Meng W, Huang X, Zhu W, Yin C, Wang C, et al. miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer. Proc Natl Acad Sci USA. 2020;117(8):4347–57.
pubmed: 32041891
pmcid: 7049122
doi: 10.1073/pnas.1917531117
Li H, Feng C, Shi S. miR-196b promotes lung cancer cell migration and invasion through the targeting of GATA6. Oncol Lett. 2018;16(1):247–52.
pubmed: 29928408
pmcid: 6006457
Chen W, Chen Z, Zhang M, Tian Y, Liu L, Lan R, et al. GATA6 exerts potent lung cancer suppressive function by inducing cell senescence. Front Oncol. 2020;10:824.
pubmed: 32596145
pmcid: 7304445
doi: 10.3389/fonc.2020.00824
Xu L, Deng S, Xiong H, Shi W, Luo S, Chen L. GATA-6 transcriptionally inhibits Shh to repress cell proliferation and migration in lung squamous cell carcinoma. Int J Biochem Cell Biol. 2019;115:105591.
pubmed: 31442607
doi: 10.1016/j.biocel.2019.105591
Xu Y, Wu H, Wu L, Xu L, Li J, Wang Q, et al. Silencing of long non-coding RNA SOX21-AS1 inhibits lung adenocarcinoma invasion and migration by impairing TSPAN8 via transcription factor GATA6. Int J Biol Macromol. 2020;164:1294–303.
pubmed: 32698071
doi: 10.1016/j.ijbiomac.2020.07.172
Arnal-Estapé A, Cai WL, Albert AE, Zhao M, Stevens LE, López-Giráldez F, et al. Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6. Oncogene. 2020;39(18):3726–37.
pubmed: 32157212
pmcid: 7190573
doi: 10.1038/s41388-020-1246-z
Zang Q, Xu L, Li J, Jia H. GATA6 activated long non-coding RNA PCAT1 maintains stemness of non-small cell lung cancer by mediating FRK. J BUON. 2020;25(5):2371–81.
pubmed: 33277858