Effect of alkylglycerone phosphate synthase on the expression levels of lncRNAs in glioma cells and its functional prediction

Chen,Lei; Zhang,Weijian; He,Lihua; Jin,Li; Qian,Liyu; Zhu,Yu

doi:10.3892/ol.2020.11927

Effect of alkylglycerone phosphate synthase on the expression levels of lncRNAs in glioma cells and its functional prediction

Authors:
- Lei Chen
- Weijian Zhang
- Lihua He
- Li Jin
- Liyu Qian
- Yu Zhu
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Affiliations: Department of Otolaryngology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China, Postgraduate School of Tianjin Medical University, Tianjin 300070, P.R. China, Integrated Chinese and Western Medicine School of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China, Department of Tumor Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, Department of Clinical Laboratory, Tianjin Haihe Hospital, Tianjin 300350, P.R. China
Published online on: July 29, 2020 https://doi.org/10.3892/ol.2020.11927
Article Number: 66
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alkylglycerone phosphate synthase (AGPS) is a key enzyme for ether ester synthesis and acts as an oncogene in malignant tumors. The present study aimed to investigate the effect of AGPS silencing on the expression levels of long non‑coding RNAs (lncRNAs) and the co‑expression with mRNAs in glioma U251 cells using microarray analysis. Furthermore, the underlying biological functions of crucial lncRNAs identified were investigated. It was discovered that in vitro U251 cell proliferation was suppressed following the genetic silencing of AGPS. Differentially expressed lncRNAs and mRNAs in U251 cells were sequenced following AGPS silencing. The results from the Gene Ontology analysis identified that the co‑expressed mRNAs were mainly involved in biological processes, such as ‘cellular response to hypoxia’, ‘extracellular matrix organization’ and ‘PERK‑mediated unfolded protein response’. In addition, Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis revealed that the co‑expressed mRNAs were the most enriched in the ‘AGE/RAGE signaling pathway in diabetic conditions’. Additionally, the PI3K/Akt and epidermal growth factor receptor signaling pathways serve important roles in tumor processes, for example carcinogenesis and angiogenesis. Furthermore, it was identified that the lncRNA AK093732 served a vital role in the regulatory network and the core pathway in this network regulated by this lncRNA was discovered to be the ‘Cytokine‑cytokine receptor interaction’. In conclusion, the findings of the present study suggested that AGPS may affect cell proliferation and the degree of malignancy. In addition, the identified lncRNAs and their co‑expressed mRNAs screened using microarrays may have significant biological effects in the occurrence, development and metastasis of glioma, and thus may be novel markers of glioma.

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1	Ferris SP, Hofmann JW, Solomon DA and Perry A: Characterization of gliomas: From morphology to molecules. Virchows Arch. 2:257–269. 2017. View Article : Google Scholar
2	Benjamin Daniel I, Cravatt Benjamin F and Nomura Daniel K: Global profiling strategies for mapping dysregulated metabolic pathways in cancer. Cell Metab. 5:565–577. 2012. View Article : Google Scholar
3	Piano V, Benjamin DI, Valente S, Nenci S, Marrocco B, Mai A, Aliverti A, Nomura DK and Mattevi A: Discovery of inhibitors for the ether lipid-generating enzyme AGPS as anti-cancer agents. ACS Chem Biol. 11:2589–2597. 2015. View Article : Google Scholar
4	Benjamin DI, Cozzo A, Ji X, Roberts LS, Louie SM, Mulvihill MM, Luo K and Nomura DK: Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity. Proc Natl Acad Sci USA. 110:14912–14917. 2013. View Article : Google Scholar : PubMed/NCBI
5	Hou S, Tan J, Yang B, He L and Zhu Y: Effect of alkylglycerone phosphate synthase on the expression profile of circRNAs in the human thyroid cancer cell line FRO. Oncol Lett. 15:7889–7899. 2018.PubMed/NCBI
6	Stazi G, Battistelli C, Piano V, Mazzone R, Marrocco B, Marchese S, Louie SM, Zwergel C, Antonini L, Patsilinakos A, et al: Development of alkyl glycerone phosphate synthase inhibitors: Structure-activity relationship and effects on ether lipids and epithelial-mesenchymal transition in cancer cells. Eur J Med Chem. 163:722–735. 2019. View Article : Google Scholar : PubMed/NCBI
7	Zhu Y, Zhu L, Lu L, Zhang L, Zhang G, Wang Q and Yang P: Role and mechanism of the alkylglycerone phosphate synthase in suppressing the invasion potential of human glioma and hepatic carcinoma cells in vitro. Oncol Rep. 32:431–436. 2014. View Article : Google Scholar : PubMed/NCBI
8	Jarroux J, Morillon A and Pinskaya M: History, discovery, and classification of lncRNAs. Adv Exp Med Biol. 1008:1–46. 2017. View Article : Google Scholar : PubMed/NCBI
9	Jiang X, Yan Y, Hu M, Chen X, Wang Y, Dai Y, Wu D, Wang Y, Zhuang Z and Xia H: Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells. J Neurosurg. 2016:129–136. 2016. View Article : Google Scholar : PubMed/NCBI
10	Lim W and Kim HS: Exosomes as therapeutic vehicles for cancer. Tissue Eng Regen Med. 16:213–223. 2019. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Noman MZ, Hasmim M, Messai Y, Terry S, Kieda C, Janji B and Chouaib S: Hypoxia: A key player in antitumor immune response. A review in the theme: Cellular responses to hypoxia. Am J Physiol Cell Physiol. 309:C569–C579. 2015. View Article : Google Scholar : PubMed/NCBI
13	Pickup MW, Mouw JK and Weaver VM: The extracellular matrix modulates the hallmarks of cancer. EMBO Rep. 15:1243–1253. 2014. View Article : Google Scholar : PubMed/NCBI
14	Soni H, Bode J, Nguyen CDL, Puccio L, Neßling M, Piro RM, Bub J, Phillips E, Ahrends R, Eipper BA, et al: PERK-mediated expression of peptidylglycine α-amidating monooxygenase supports angiogenesis in glioblastoma. Oncogenesis. 9:182020. View Article : Google Scholar : PubMed/NCBI
15	Wood R and Snyder F: Characterization and identification of glyceryl ether diesters present in tumor cells. J Lipid Res. 8:494–500. 1967.PubMed/NCBI
16	Jaffrès PA, Gajate C, Bouchet AM, Couthon-Gourvès H, Chantôme A, Potier-Cartereau M, Besson P, Bougnoux P, Mollinedo F and Vandier C: Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy. Pharmacol Ther. 165:114–131. 2016. View Article : Google Scholar : PubMed/NCBI
17	Li Y, Han X, Feng H and Han J: Long noncoding RNA OIP5-AS1 in cancer. Clin Chim Acta. 499:75–80. 2019. View Article : Google Scholar : PubMed/NCBI
18	Shen J, Cao B, Wang Y, Ma C, Zeng Z, Liu L, Li X, Tao D, Gong J and Xie D: Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1/FAK signalling in breast cancer. J Exp Clin Cancer Res. 37:1752018. View Article : Google Scholar : PubMed/NCBI
19	Wu P, Wang Y, Wu Y, Jia Z, Song Y and Liang N: Expression and prognostic analyses of ITGA11, ITGB4 and ITGB8 in human non-small cell lung cancer. PeerJ. 7:e82992019. View Article : Google Scholar : PubMed/NCBI
20	Jeong BY, Cho KH, Jeong KJ, Park YY, Kim JM, Rha SY, Park CG, Mills GB, Cheong JH and Lee HY: Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin. Exp Mol Med. 50:e4352018. View Article : Google Scholar : PubMed/NCBI
21	Zeng B, Zhou M, Wu H and Xiong Z: SPP1 promotes ovarian cancer progression via Integrin β1/FAK/AKT signaling pathway. Onco Targets Ther. 11:1333–1343. 2018. View Article : Google Scholar : PubMed/NCBI
22	Rhead B, Shao X, Quach H, Ghai P, Barcellos LF and Bowcock AM: Global expression and CpG methylation analysis of primary endothelial cells before and after TNFa stimulation reveals gene modules enriched in inflammatory and infectious diseases and associated DMRs. PLoS One. 15:e02308842020. View Article : Google Scholar : PubMed/NCBI
23	Ni M, Liu X, Meng Z, Liu S, Jia S, Liu Y, Zhou W, Wu J, Zhang J, Guo S, et al: A bioinformatics investigation into the pharmacological mechanisms of javanica oil emulsion injection in non-small cell lung cancer based on network pharmacology methodologies. BMC Complement Med Ther. 20:1742020. View Article : Google Scholar : PubMed/NCBI
24	Long Y, Wang X, Youmans DT and Cech TR: How do lncRNAs regulate transcription? Sci Adv. 3:eaao21102017. View Article : Google Scholar : PubMed/NCBI
25	Abedini P, Fattahi A, Agah S, Talebi A, Beygi AH, Amini SM, Mirzaei A and Akbari A: Expression analysis of circulating plasma long noncoding RNAs in colorectal cancer: The relevance of lncRNAs ATB and CCAT1 as potential clinical hallmarks. J Cell Physiol. 234:22028–22033. 2019. View Article : Google Scholar : PubMed/NCBI
26	Liang WC, Ren JL, Wong CW, Chan SO, Waye MM, Fu WM and Zhang JF: LncRNA-NEF antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/β-catenin signaling. Oncogene. 37:1445–1456. 2018. View Article : Google Scholar : PubMed/NCBI
27	Wang B, Xian J, Zang J, Xiao L, Li Y, Sha M and Shen M: Long non-coding RNA FENDRR inhibits proliferation and invasion of hepatocellular carcinoma by down-regulating glypican-3 expression. Biochem Biophys Res Commun. 509:143–147. 2019. View Article : Google Scholar : PubMed/NCBI
28	Zhang G, Han G, Zhang X, Yu Q, Li Z, Li Z and Li J: Long non-coding RNA FENDRR reduces prostate cancer malignancy by competitively binding miR-18a-5p with RUNX1. Biomarkers. 23:435–445. 2018. View Article : Google Scholar : PubMed/NCBI
29	Liu J and Du W: LncRNA FENDRR attenuates colon cancer progression by repression of SOX4 protein. Onco Targets Ther 12: 4287-4295, 2019; Li Y, Zhang W, Liu P, Xu Y, Tang L, Chen W and Guan X: Long non-coding RNA FENDRR inhibits cell proliferation and is associated with good prognosis in breast cancer. Onco Targets Ther. 11:1403–1412. 2018.PubMed/NCBI
30	Xu R and Han Y: Long non-coding RNA FOXF1 adjacent non-coding developmental regulatory RNA inhibits growth and chemotherapy resistance in non-small cell lung cancer. Arch Med Sci. 15:1539–1546. 2019. View Article : Google Scholar : PubMed/NCBI
31	Gong F, Dong D, Zhang T and Xu W: Long non-coding RNA FENDRR attenuates the stemness of non-small cell lung cancer cells via decreasing multidrug resistance gene 1 (MDR1) expression through competitively binding with RNA binding protein HuR. Eur J Pharmacol. 853:345–352. 2019. View Article : Google Scholar : PubMed/NCBI
32	Navarro G, Martínez-Pinilla E, Sánchez-Melgar A, Ortiz R, Noé V, Martín M, Ciudad C and Franco R: A genomics approach identifies selective effects of trans-resveratrol in cerebral cortex neuron and glia gene expression. PLoS One. 12:e01760672017. View Article : Google Scholar : PubMed/NCBI
33	Lee EJ, Rath P, Liu J, Ryu D, Pei L, Noonepalle SK, Shull AY, Feng Q, Litofsky NS, Miller DC, et al: Identification of global DNA methylation signatures in glioblastoma-derived cancer stem cells. J Genet Genomics. 42:355–371. 2015. View Article : Google Scholar : PubMed/NCBI
34	Shen Z, Li Q, Deng H, Lu D, Song H and Guo J: Long non-coding RNA profiling in laryngeal squamous cell carcinoma and its clinical significance: Potential biomarkers for LSCC. PLoS One. 9:e1082372014. View Article : Google Scholar : PubMed/NCBI