miRNA array analysis of plasma miRNA alterations in rats exposed to a high altitude hypoxic environment

Chen,Feng; Wang,Ren‑Jie; Li,Guang‑Zong; Zhang,Yi; Yu,Shuo; Liu,Ying‑Fu; Chen,Xiao‑Yi; Hou,Shi‑Ke

doi:10.3892/mmr.2018.9570

miRNA array analysis of plasma miRNA alterations in rats exposed to a high altitude hypoxic environment

Authors:
- Feng Chen
- Ren‑Jie Wang
- Guang‑Zong Li
- Yi Zhang
- Shuo Yu
- Ying‑Fu Liu
- Xiao‑Yi Chen
- Shi‑Ke Hou
View Affiliations

Affiliations: Graduate School, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Neurosurgery, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China, Key Laboratory of Disaster and Emergency Rescue Medicine in People's Liberation Army, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China , Department of Cell Biology, Logistics University of Chinese People's Armed Police Forces, Tianjin 300309, P.R. China
Published online on: October 22, 2018 https://doi.org/10.3892/mmr.2018.9570
Pages: 5502-5510
Copyright: © Chen 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

In the present study, the microRNA (miRNA) expression profiles of rats exposed to high altitude hypoxia and normal conditions were obtained from miRNA array analysis. Bioinformatics analyses, including the use of the Gene Oncology and Kyoto Encyclopedia of Genes and Genomes databases, were used to identify the genes and pathways, which were specifically associated with high altitude hypoxic environment‑associated miRNAs. A total of 26 miRNAs were differentially expressed in the two groups, comprising six upregulated and 20 downregulated miRNAs. In the present study, a novel pattern of upregulated miRNAs and their associated pathways were constructed, including proteoglycans in cancer, spliceosome, gluamatergic synapse, glycolysis/gluconeogenesis, Foxo, cGMP‑PKG and p53 signaling pathways, which may provide novel targets for diagnosing and understanding the mechanism of high altitude hypoxia‑induced disease.

View Figures

View References

1	Sherpa LY, Deji, Stigum H, Chongsuvivatwong V, Thelle DS and Bjertness E: Obesity in Tibetans aged 30–30 living at different altitudes under the north and south faces of Mt. Everest. Int J Environ Res Public Health. 7:1670–80. 2010. View Article : Google Scholar : PubMed/NCBI
2	Windsor JS and Rodway GW: Rodway, Heights and haematology: The story of haemoglobin at altitude. Postgrad Med J. 83:148–151. 2007. View Article : Google Scholar : PubMed/NCBI
3	Peyssonnaux C, Nizet V and Johnson RS: Role of the hypoxia inducible factors HIF in iron metabolism. Cell Cycle. 7:28–32. 2008. View Article : Google Scholar : PubMed/NCBI
4	Recavarren-Arce S, Ramirez-Ramos A, Gilman RH, Chinga-Alayo E, Watanabe-Yamamoto J, Rodriguez-Ulloa C, Miyagui J, Passaro DJ and Eza D: Severe gastritis in the Peruvian Andes. Histopathology. 46:374–379. 2005. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, et al: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105:10513–10518. 2008. View Article : Google Scholar : PubMed/NCBI
7	Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, et al: Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18:997–1006. 2008. View Article : Google Scholar : PubMed/NCBI
8	Meder B, Backes C, Haas J, Leidinger P, Stähler C, Großmann T, Vogel B, Frese K, Giannitsis E, Katus HA, et al: Influence of the confounding factors age and sex on microRNA profiles from peripheral blood. Clin Chem. 60:1200–1208. 2014. View Article : Google Scholar : PubMed/NCBI
9	Yan Y, Shi Y, Wang C, Guo P, Wang J, Zhang CY and Zhang C: Influence of a high-altitude hypoxic environment on human plasma microRNA profiles. Sci Rep. 5:151562015. View Article : Google Scholar : PubMed/NCBI
10	Su X, Song Y, Jiang J and Bai C: The role of aquaporin-1 (AQP1) expression in a murine model of lipopolysaccharide-induced acute lung injury. Respir Physiol Neurobiol. 142:1–11. 2004. 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	Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC and Lempicki RA: DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4:P32003. View Article : Google Scholar : PubMed/NCBI
13	Dupuy D, Bertin N, Hidalgo CA, Venkatesan K, Tu D, Lee D, Rosenberg J, Svrzikapa N, Blanc A, Carnec A, et al: Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans. Nat Biotechnol. 25:663–668. 2007. View Article : Google Scholar : PubMed/NCBI
14	Michel RP, Hakim TS, Smith TT and Poulsen RS: Quantitative morphology of permeability lung edema in dogs induced by alpha-naphthylthiourea. Lab Invest. 49:412–419. 1983.PubMed/NCBI
15	Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, et al: A microRNA signature of hypoxia. Mol Cell Biol. 27:1859–1867. 2007. View Article : Google Scholar : PubMed/NCBI
16	Liang H, Studach L, Hullinger RL, Xie J and Andrisani OM: Down-regulation of RE-1 silencing transcription factor (REST) in advanced prostate cancer by hypoxia-induced miR-106b~25. Exp Cell Res. 320:188–199. 2014. View Article : Google Scholar : PubMed/NCBI
17	Caruso P, MacLean MR, Khanin R, McClure J, Soon E, Southgate M, MacDonald RA, Greig JA, Robertson KE, Masson R, et al: Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler Thromb Vasc Biol. 30:716–723. 2010. View Article : Google Scholar : PubMed/NCBI
18	Shi XF, Wang H, Xiao FJ, Yin Y, Xu QQ, Ge RL and Wang LS: MiRNA-486 regulates angiogenic activity and survival of mesenchymal stem cells under hypoxia through modulating Akt signal. Biochem Biophys Res Commun. 470:670–677. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zhang B, Zhou M, Li C, Zhou J, Li H, Zhu D, Wang Z, Chen A and Zhao Q: MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7. PLoS One. 9:e1002982014. View Article : Google Scholar : PubMed/NCBI
20	Lovering RC, Camon EB, Blake JA and Diehl AD: Access to immunology through the Gene Ontology. Immunology. 125:154–160. 2008. View Article : Google Scholar : PubMed/NCBI
21	Wang Y, Yang L, Wu B, Song Z and He S: Transcriptome analysis of the plateau fish (Triplophysa dalaica): Implications for adaptation to hypoxia in fishes. Gene. 565:211–220. 2015. View Article : Google Scholar : PubMed/NCBI
22	Yang Y, Wang L, Han J, Tang X, Ma M, Wang K, Zhang X, Ren Q, Chen Q and Qiu Q: Comparative transcriptomic analysis revealed adaptation mechanism of Phrynocephalus erythrurus, the highest altitude Lizard living in the Qinghai-Tibet Plateau. BMC Evol Bio. 15:1012015. View Article : Google Scholar
23	Butler PJ and Jones DR: Physiology of diving of birds and mammals. Physiol Rev. 77:837–899. 1997. View Article : Google Scholar : PubMed/NCBI
24	Denko NC: Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 8:705–713. 2008. View Article : Google Scholar : PubMed/NCBI
25	Semenza GL: Hypoxia-inducible factors in physiology and medicine. Cell. 148:399–408. 2012. View Article : Google Scholar : PubMed/NCBI
26	Bakker WJ, Harris IS and Mak TW: FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2. Mol Cell. 28:941–953. 2007. View Article : Google Scholar : PubMed/NCBI
27	Wang B, Zhang YB, Zhang F, Lin H, Wang X, Wan N, Ye Z, Weng H, Zhang L, Li X, et al: On the origin of Tibetans and their genetic basis in adapting high-altitude environments. PLoS One. 6:e170022011. View Article : Google Scholar : PubMed/NCBI
28	Yu J, Liu XW and Kim HR: Platelet-derived growth factor (PDGF) receptor-alpha-activated c-Jun NH2-terminal kinase-1 is critical for PDGF-induced p21WAF1/CIP1 promoter activity independent of p53. J Biol Chem. 278:49582–49588. 2003. View Article : Google Scholar : PubMed/NCBI
29	Mizuno S, Bogaard HJ, Voelkel NF, Umeda Y, Kadowaki M, Ameshima S, Miyamori I and Ishizaki T: Hypoxia regulates human lung fibroblast proliferation via p53-dependent and -independent pathways. Respir Res. 10:172009. View Article : Google Scholar : PubMed/NCBI
30	Mizuno S, Bogaard HJ, Kraskauskas D, Alhussaini A, Gomez-Arroyo J, Voelkel NF and Ishizaki T: p53 Gene deficiency promotes hypoxia-induced pulmonary hypertension and vascular remodeling in mice. Am J Physiol Lung Cell Mol Physiol. 300:L753–L761. 2011. View Article : Google Scholar : PubMed/NCBI
31	Gao Y, Dhanakoti S, Trevino EM, Sander FC, Portugal AM and Raj JU: Effect of oxygen on cyclic GMP-dependent protein kinase-mediated relaxation in ovine fetal pulmonary arteries and veins. Am J Physiol Lung Cell Mol Physiol. 285:L611–L618. 2003. View Article : Google Scholar : PubMed/NCBI
32	Gao Y, Portugal AD, Negash S, Zhou W, Longo LD and Usha Raj J: Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia. Am J Physiol Lung Cell Mol Physiol. 292:L678–L684. 2007. View Article : Google Scholar : PubMed/NCBI
33	Jernigan NL and Resta TC: Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation. Am J Physiol Lung Cell Mol Physiol. 282:L1366–L1375. 2002. View Article : Google Scholar : PubMed/NCBI