LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human thoracic aortic dissection

Li,Yang; Yang,Nan; Zhou,Xianbao; Bian,Xuezhi; Qiu,Genqiang; Zhang,Mo; Lin,Huagang; Li,Dingfeng

doi:10.3892/mmr.2018.9308

LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human thoracic aortic dissection

Authors:
- Yang Li
- Nan Yang
- Xianbao Zhou
- Xuezhi Bian
- Genqiang Qiu
- Mo Zhang
- Huagang Lin
- Dingfeng Li
View Affiliations

Affiliations: Department of General Surgery, Beijing Yuho Rehabilitation Hospital of Integrated Chinese and Western Medicine, Beijing 100039, P.R. China, Department of Stomatology, PLA 309th Hospital, Beijing 100091, P.R. China, Department of Orthopedics, Beijing Yuho Rehabilitation Hospital of Integrated Chinese and Western Medicine, Beijing 100039, P.R. China
Published online on: July 23, 2018 https://doi.org/10.3892/mmr.2018.9308
Pages: 3167-3176
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to determine the potential core genes in the pathogenesis of human thoracic aortic dissection (TAD) by analyzing microarray profiles of long non‑coding (lnc)‑RNAs between TAD and normal thoracic aorta (NTA). The differentially expressed lncRNA profiles of the aorta tissues between TAD patients (TAD group, n=6) and age‑matched donors with aortic diseases (NTA group, n=6) were analyzed by lncRNAs microarray. Gene ontology (GO), pathway and network analyses were used to further investigate candidate lncRNAs and mRNAs. Differentially expressed lncRNAs and mRNAs were validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In total, the present study identified 765 lncRNAs and 619 mRNAs with differential expression between TAD and NTA (fold change >2.0, P<0.01). GO analysis demonstrated that the differentially upregulated lncRNAs are associated with cell differentiation, homeostasis, cell growth and angiogenesis. Kyoto Encyclopedia of Gene and Genomes pathway analysis demonstrated that the differentially downregulated lncRNAs are mainly associated with arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy and dilated cardiomyopathy. To reduce the lncRNAs for further investigation and to enrich those potentially involved in TAD, a total of 16 candidate lncRNAs with a significant expression (fold change >4, P<0.01) were selected, that were associated with an annotated protein‑coding gene through the GO term and scientific literatures. Then a set of significantly expressed lncRNAs [purinergic receptor P2X7 (P2RX7), hypoxia inducing factor (HIF)‑1A‑AS2, AX746823, RP11‑69I8.3 and RP11‑536K7.5) and the corresponding mRNAs (P2RX7, cyclin dependent kinase inhibitor 2B, HIF‑1A, runt‑related transcription factor 1, connective tissue growth factor and interleukin 2 receptor a chain] were confirmed using RT‑qPCR. The present study revealed that the expression profiles of lncRNAs and mRNAs in aorta tissues from TAD were significantly altered. These results may provide important insights into the pathogenesis of TAD disease.

View Figures

View References

1	Clouse WD, Hallett JW Jr, Schaff HV, Spittell PC, Rowland CM, Ilstrup DM and Melton LJ III: Acute aortic dissection: Population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc. 79:176–180. 2004. View Article : Google Scholar : PubMed/NCBI
2	Leitman IM, Suzuki K, Wengrofsky AJ, Menashe E, Poplawski M, Woo KM, Geller CM, Lucido D, Bernik T, Zeifer BA and Patton B: Early recognition of acute thoracic aortic dissection and aneurysm. World J Emerg Surg. 8:472013. View Article : Google Scholar : PubMed/NCBI
3	Batista PJ and Chang HY: Long noncoding RNAs: Cellular address codes in development and disease. Cell. 152:1298–1307. 2013. View Article : Google Scholar : PubMed/NCBI
4	Kornienko AE, Guenzl PM, Barlow DP and Pauler FM: Gene regulation by the act of long non-coding RNA transcription. BMC Biol. 11:592013. View Article : Google Scholar : PubMed/NCBI
5	Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, et al: Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet. 51:1087–1099. 2006. View Article : Google Scholar : PubMed/NCBI
6	Miner GH, Faries PL, Costa KD, Hanss BG and Marin ML: An update on the etiology of abdominal aortic aneurysms: Implications for future diagnostic testing. Expert Rev Cardiovasc Ther. 13:1079–1090. 2015. View Article : Google Scholar : PubMed/NCBI
7	He Q, Tan J, Yu B, Shi W and Liang K: Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: Implications for the pathogenesis of thoracoabdominal aorta aneurysm. Pharmazie. 70:310–315. 2015.PubMed/NCBI
8	Wang S, Zhang X, Yuan Y, Tan M, Zhang L, Xue X, Yan Y, Han L and Xu Z: BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro. Eur J Cardiothorac Surg. 47:439–446. 2015. View Article : Google Scholar : PubMed/NCBI
9	Duggirala A, Delogu F, Angelini TG, Smith T, Caputo M, Rajakaruna C and Emanueli C: Non coding RNAs in aortic aneurysmal disease. Front Genet. 6:1252015. View Article : Google Scholar : PubMed/NCBI
10	ENCODE Project Consortium, . Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, et al: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 447:799–816. 2007. View Article : Google Scholar : PubMed/NCBI
11	Dudzinski DM and Isselbacher EM: Diagnosis and management of thoracic aortic disease. Curr Cardiol Rep. 17:1062015. View Article : Google Scholar : PubMed/NCBI
12	Papait R, Kunderfranco P, Stirparo GG, Latronico MV and Condorelli G: Long noncoding RNA: A new player of heart failure? J Cardiovasc Transl Res. 6:876–883. 2013. View Article : Google Scholar : PubMed/NCBI
13	Liu L, An X, Li Z, Song Y, Li L, Zuo S, Liu N, Yang G, Wang H, Cheng X, et al: The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy. Cardiovasc Res. 111:56–65. 2016. View Article : Google Scholar : PubMed/NCBI
14	Zhao Y, Feng G, Wang Y, Yue Y and Zhao W: Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: Implications for TAA pathogenesis. Int J Clin Exp Pathol. 7:7643–7652. 2014.PubMed/NCBI
15	Magistri M, Faghihi MA, St Laurent G III and Wahlestedt C: Regulation of chromatin structure by long noncoding RNAs: Focus on natural antisense transcripts. Trends Genet. 28:389–396. 2012. View Article : Google Scholar : PubMed/NCBI
16	Leung A, Trac C, Jin W, Lanting L, Akbany A, Sætrom P, Schones DE and Natarajan R: Novel long noncoding RNAs are regulated by angiotensin II in vascular smooth muscle cells. Circ Res. 113:266–278. 2013. View Article : Google Scholar : PubMed/NCBI
17	Freedman JE and Miano JM: National Heart, Lung, and Blood Institute Workshop Participants*: Challenges and opportunities in linking long noncoding RNAs to cardiovascular, lung, and blood diseases. Arterioscler Thromb Vasc Biol. 37:21–25. 2017. View Article : Google Scholar : PubMed/NCBI
18	Huang DW, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar : PubMed/NCBI
19	Liu K, Fang C, Shen Y, Liu Z, Zhang M, Ma B and Pang X: Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular smooth muscle cell through PI3K/AKT/AEG-1 signaling. Oncotarget. 8:33343–33352. 2017.PubMed/NCBI
20	Ungvari Z, Valcarcel-Ares MN, Tarantini S, Yabluchanskiy A, Fülöp GA, Kiss T and Csiszar A: Connective tissue growth factor (CTGF) in age-related vascular pathologies. Geroscience. 39:491–498. 2017. View Article : Google Scholar : PubMed/NCBI
21	Sachdeva J, Mahajan A, Cheng J, Baeten JT, Lilly B, Kuivaniemi H and Hans CP: Smooth muscle cell-specific Notch1 haploinsufficiency restricts the progression of abdominal aortic aneurysm by modulating CTGF expression. PLoS One. 12:e01785382017. View Article : Google Scholar : PubMed/NCBI
22	Leeper NJ, Raiesdana A, Kojima Y, Kundu RK, Cheng H, Maegdefessel L, Toh R, Ahn GO, Ali ZA, Anderson DR, et al: Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arterioscler Thromb Vasc Biol. 33:e1–e10. 2013. View Article : Google Scholar : PubMed/NCBI
23	Chiao CW, Tostes RC and Webb RC: P2X7 receptor activation amplifies lipopolysaccharide-induced vascular hyporeactivity via interleukin-1 beta release. J Pharmacol Exp Ther. 326:864–870. 2008. View Article : Google Scholar : PubMed/NCBI
24	Chiao CW, da Silva-Santos JE, Giachini FR, Tostes RC, Su MJ and Webb RC: P2X7 receptor activation contributes to an initial upstream mechanism of lipopolysaccharide-induced vascular dysfunction. Clin Sci (Lond). 125:131–141. 2013. View Article : Google Scholar : PubMed/NCBI
25	Pahl MC, Erdman R, Kuivaniemi H, Lillvis JH, Elmore JR and Tromp G: Transcriptional (ChIP-Chip) analysis of ELF1, ETS2, RUNX1 and STAT5 in human abdominal aortic aneurysm. Int J Mol Sci. 16:11229–11258. 2015. View Article : Google Scholar : PubMed/NCBI
26	Li L, Yang SH, Yao Y, Xie YQ, Yang YQ, Wang YH, Yin XY, Ma HD, Gershwin M and Lian ZX: Block of both TGF-β and IL-2 signaling impedes Neurophilin-1+ regulatory T cell and follicular regulatory T cell development. Cell Death Dis. 7:e24392016. View Article : Google Scholar : PubMed/NCBI
27	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar : PubMed/NCBI
28	Jiang X and Ning Q: The emerging roles of long noncoding RNAs in common cardiovascular diseases. Hypertens Res. 38:375–379. 2015. View Article : Google Scholar : PubMed/NCBI