Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury

Jiang,Yong; Zhu,Feng; Wu,Guo‑Sheng; Wang,Kang‑An; Wang,Chen; Yu,Qing; Zhu,Bang‑Hui; Sun,Yu; Xia,Zhao‑Fan

doi:10.3892/etm.2020.8686

Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury

Authors:
- Yong Jiang
- Feng Zhu
- Guo‑Sheng Wu
- Kang‑An Wang
- Chen Wang
- Qing Yu
- Bang‑Hui Zhu
- Yu Sun
- Zhao‑Fan Xia
View Affiliations

Affiliations: Department of Burn Surgery, Changhai Hospital, Navy Medical University, Shanghai 200433, P.R. China
Published online on: April 23, 2020 https://doi.org/10.3892/etm.2020.8686
Pages: 227-234
Copyright: © Jiang 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

Acute lung injury (ALI) and respiratory distress syndrome are common, potentially lethal injuries that predominantly occur following chest trauma. Circular RNAs (circRNAs) are stable conserved non‑coding RNAs that are widely expressed in different organs. To the best of our knowledge, no previous studies have shown whether circRNAs are involved in traumatic lung injury (TLI). The aim of the present study was to identify highly expressed circRNAs in plasma samples from patients with TLI and explore their potential functions in the pathogenesis of TLI. A high‑throughput circRNA microarray was used to investigate the expression profile of circRNAs in plasma samples from five patients with TLI and paired control samples. Subsequently, a total of five abnormally expressed circRNAs were investigated using reverse transcription‑quantitative PCR (RT‑qPCR). A bioinformatics analysis was performed to predict a competitive endogenous RNA (ceRNA) network. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the main biological processes and pathways. Finally, additional samples were tested to identify the expression profiles of the selected circRNAs. Among the 310 circRNAs that were highly expressed in the microarray analysis, 60 were upregulated and 250 were downregulated in patients with TLI. RT‑qPCR results indicated that two downregulated circRNAs (circ_102927 and circ_100562) and one upregulated circRNA (circ_101523) matched the microarray results. The bioinformatics analysis constructed a targeting network based on the three validated circRNAs. GO and KEGG analyses identified the top ten enriched annotations. The expression of homo sapiens circular RNA 102927 (hsa_circRNA_102927) in the plasma of patients with TLI was 0.34‑fold compared with the control group in expanded size validation. The results of the present study identified the differentially expressed circRNAs in the plasma of patients with TLI and provided evidence that highly expressed circRNAs involved in the ceRNA network may serve a role in the pathophysiology of TLI.

View Figures

View References

1	Wu XJ, Xia ZY, Wang LL, Luo T, Zhan LY, Meng QT and Song XM: Effects of penehyclidine hydrochloride on pulmonary contusion from blunt chest trauma in rats. Injury. 43:232–236. 2012.PubMed/NCBI View Article : Google Scholar
2	Balci AE, Kazez A, Eren S, Ayan E, Ozalp K and Eren MN: Blunt thoracic trauma in children: Review of 137 cases. Eur J Cardiothorac Surg. 26:387–392. 2004.PubMed/NCBI View Article : Google Scholar
3	Gaillard M, Herve C, Mandin L and Raynaud P: Mortality prognostic factors in chest injury. J Trauma. 30:93–96. 1990.PubMed/NCBI View Article : Google Scholar
4	Calfee CS, Eisner MD, Ware LB, Thompson BT, Parsons PE, Wheeler AP, Korpak A and Matthay MA: Acute Respiratory Distress Syndrome Network National Heart Lung and Blood Institute: Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders. Crit Care Med. 35:2243–2250. 2007.PubMed/NCBI View Article : Google Scholar
5	Suresh MV, Yu B, Lakshminrusimha S, Machado-Aranda D, Talarico N, Zeng L, Davidson BA, Pennathur S and Raghavendran K: The protective role of MnTBAP in oxidant-mediated injury and inflammation in a rat model of lung contusion. Surgery. 154:980–990. 2013.PubMed/NCBI View Article : Google Scholar
6	Van Eeden SF, Klopper JF, Alheit B and Bardin PG: Ventilation-perfusion imaging in evaluating regional lung function in nonpenetrating injury to the chest. Chest. 95:632–638. 1989.PubMed/NCBI View Article : Google Scholar
7	Cohn SM: Pulmonary contusion: Review of the clinical entity. J Trauma. 42:973–979. 1997.PubMed/NCBI View Article : Google Scholar
8	Klein Y, Cohn SM and Proctor KG: Lung contusion: Pathophysiology and management. Curr Opin Anaesthesiol. 15:65–68. 2002.PubMed/NCBI View Article : Google Scholar
9	Suresh MV, Thomas B, Machado-Aranda D, Dolgachev VA, Kumar Ramakrishnan S, Talarico N, Cavassani K, Sherman MA, Hemmila MR, Kunkel SL, et al: Double-stranded RNA interacts with toll-like receptor 3 in driving the acute inflammatory response following lung contusion. Crit Care Med. 44:e1054–e1066. 2016.PubMed/NCBI View Article : Google Scholar
10	Ebbesen KK, Hansen TB and Kjems J: Insights into circular RNA biology. RNA Biol. 14:1035–1045. 2017.PubMed/NCBI View Article : Google Scholar
11	Ledford H: Circular RNAs throw genetics for a loop. Nature. 494(415)2013.PubMed/NCBI View Article : Google Scholar
12	Hsiao KY, Sun HS and Tsai SJ: Circular RNA-New member of noncoding RNA with novel functions. Exp Biol Med (Maywood). 242:1136–1141. 2017.PubMed/NCBI View Article : Google Scholar
13	Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF and Sharpless NE: Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19:141–157. 2013.PubMed/NCBI View Article : Google Scholar
14	Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013.PubMed/NCBI View Article : Google Scholar
15	Kulcheski FR, Christoff AP and Margis R: Circular RNAs are miRNA sponges and can be used as a new class of biomarker. J Biotechnol. 238:42–51. 2016.PubMed/NCBI View Article : Google Scholar
16	Zhang S, Zeng X, Ding T, Guo L, Li Y, Ou S and Yuan H: Microarray profile of circular RNAs identifies hsa_circ_0014130 as a new circular RNA biomarker in non-small cell lung cancer. Sci Rep. 8(2878)2018.PubMed/NCBI View Article : Google Scholar
17	Huang WJ, Wang Y, Liu S, Yang J, Guo SX, Wang L, Wang H and Fan YF: Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression. Cancer Lett. 422:70–80. 2018.PubMed/NCBI View Article : Google Scholar
18	Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M, et al: Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 66:1151–1164. 2017.PubMed/NCBI View Article : Google Scholar
19	Huang ZK, Yao FY, Xu JQ, Deng Z, Su RG, Peng YP, Luo Q and Li JM: Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from active tuberculosis patients. Cell Physiol Biochem. 45:1230–1240. 2018.PubMed/NCBI View Article : Google Scholar
20	Guo W, Zhang B, Mu K, Feng SQ, Dong ZY, Ning GZ, Li HR, Liu S, Zhao L, Li Y, et al: Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk. Cell Death Dis. 9(319)2018.PubMed/NCBI View Article : Google Scholar
21	Wicky S, Wintermark M, Schnyder P, Capasso P and Denys A: Imaging of blunt chest trauma. Eur Radiol. 10:1524–1538. 2000.PubMed/NCBI View Article : Google Scholar
22	Jiang Y, Brynskikh AM, S-Manickam D and Kabanov AV: SOD1 nanozyme salvages ischemic brain by locally protecting cerebral vasculature. J Control Release. 213:36–44. 2015.PubMed/NCBI View Article : Google Scholar
23	Jiang Y, Arounleut P, Rheiner S, Bae Y, Kabanov AV, Milligan C and Manickam DS: SOD1 nanozyme with reduced toxicity and MPS accumulation. J Control Release. 231:38–49. 2016.PubMed/NCBI View Article : Google Scholar
24	Jiang Y, Fay JM, Poon CD, Vinod N, Zhao Y, Bullock K, Qin S, Manickam DS, Yi X, Banks WA and Kabanov AV: Nanoformulation of brain-derived neurotrophic factor with target receptor-triggered-release in the central nervous system. Adv Funct Mater. 28(1703982)2018.PubMed/NCBI View Article : Google Scholar
25	Natarajan G, Perriotte-Olson C, Bhinderwala F, Powers R, Desouza CV, Talmon GA, Yuhang J, Zimmerman MC, Kabanov AV and Saraswathi V: Nanoformulated copper/zinc superoxide dismutase exerts differential effects on glucose vs lipid homeostasis depending on the diet composition possibly via altered AMPK signaling. Transl Res. 188:10–26. 2017.PubMed/NCBI View Article : Google Scholar
26	Jiang Y, Gaudin A, Zhang J, Agarwal T, Song E, Kauffman AC, Tietjen GT, Wang Y, Jiang Z, Cheng CJ and Saltzman WM: A ‘top-down’ approach to actuate poly(amine-co-ester) terpolymers for potent and safe mRNA delivery. Biomaterials. 176:122–130. 2018.PubMed/NCBI View Article : Google Scholar
27	Singh M, George AK, Homme RP, Majumder A, Laha A, Sandhu HS and Tyagi SC: Expression analysis of the circular RNA molecules in the human retinal cells treated with homocysteine. Curr Eye Res. 44:287–293. 2019.PubMed/NCBI View Article : Google Scholar
28	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.PubMed/NCBI View Article : Google Scholar
29	Ferruelo A, Penuelas O and Lorente JA: MicroRNAs as biomarkers of acute lung injury. Ann Transl Med. 6(34)2018.PubMed/NCBI View Article : Google Scholar
30	Suresh MV, Thomas B, Dolgachev VA, Sherman MA, Goldberg R, Johnson M, Chowdhury A, Machado-Aranda D and Raghavendran K: Toll-like receptor-9 (TLR9) is requisite for acute inflammatory response and injury following lung contusion. Shock. 46:412–419. 2016.PubMed/NCBI View Article : Google Scholar
31	Cohn SM and Dubose JJ: Pulmonary contusion: An update on recent advances in clinical management. World J Surg. 34:1959–1970. 2010.PubMed/NCBI View Article : Google Scholar
32	Xia B, Lu J, Wang R, Yang Z, Zhou X and Huang P: miR-21-3p Regulates influenza A virus replication by targeting histone deacetylase-8. Front Cell Infect Microbiol. 8(175)2018.PubMed/NCBI View Article : Google Scholar