Unraveling the Molecular Mechanisms of Hyperlipidemia Using Integrated LncRNA and MRNA Microarray Data

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2022 Jan 24

PMID 35069841

Authors

Bianling Xu

Nan Wang

Xuegong Xu

Yongmin Cai

Affiliations

Soon will be listed here.

Abstract

Long non-coding RNAs (lncRNAs) have key roles in various diseases; however, their functions in hyperlipidemia (HLP) have remained elusive. In the present study, microarray technology was utilized to analyze the differential expression of lncRNAs and mRNAs in liver tissues of apolipoprotein E mice as a model of HLP compared with control mice. A total of 104 and 96 differentially expressed lncRNAs and mRNAs, respectively, were identified. Differentially expressed genes were significantly enriched in biological processes such as nitric oxide biosynthesis, innate immune response and inflammatory response. Finally, two pairs of target genes and 38 transcription factors with regulatory functions in HLP were predicted based on the lncRNA and mRNA co-expression network. The lncRNA expression profile was significantly altered in liver tissues of the mouse model of HLP and may provide novel targets for research into treatments.

References

Tosheska Trajkovska K, Topuzovska S . High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol. Anatol J Cardiol. 2017; 18(2):149-154. PMC: 5731265. DOI: 10.14744/AnatolJCardiol.2017.7608. View

Singhai A, Wakefield D, Bryant K, Hammes S, Holowka D, Baird B . Spatially defined EGF receptor activation reveals an F-actin-dependent phospho-Erk signaling complex. Biophys J. 2014; 107(11):2639-51. PMC: 4255200. DOI: 10.1016/j.bpj.2014.09.048. View

Coulthard L, Hawksworth O, Woodruff T . Complement: The Emerging Architect of the Developing Brain. Trends Neurosci. 2018; 41(6):373-384. DOI: 10.1016/j.tins.2018.03.009. View

Ozay R, Uzar E, Aktas A, Erkmen Uyar M, Gurer B, Evliyaoglu O . The role of oxidative stress and inflammatory response in high-fat diet induced peripheral neuropathy. J Chem Neuroanat. 2014; 55:51-7. DOI: 10.1016/j.jchemneu.2013.12.003. View

Chen J, Cui X, Shi C, Chen L, Yang L, Pang L . Differential lncRNA expression profiles in brown and white adipose tissues. Mol Genet Genomics. 2014; 290(2):699-707. DOI: 10.1007/s00438-014-0954-x. View

Kowarik M, Cepok S, Sellner J, Grummel V, Weber M, Korn T . CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation. 2012; 9:93. PMC: 3418196. DOI: 10.1186/1742-2094-9-93. View

Smekalova E, Kotelevtsev Y, Leboeuf D, Shcherbinina E, Fefilova A, Zatsepin T . lncRNA in the liver: Prospects for fundamental research and therapy by RNA interference. Biochimie. 2016; 131:159-172. DOI: 10.1016/j.biochi.2016.06.007. View

Zadjali F, Santana-Farre R, Vesterlund M, Carow B, Mirecki-Garrido M, Hernandez-Hernandez I . SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB J. 2012; 26(8):3282-91. DOI: 10.1096/fj.12-205583. View

Hirose T, Mishima Y, Tomari Y . Elements and machinery of non-coding RNAs: toward their taxonomy. EMBO Rep. 2014; 15(5):489-507. PMC: 4210095. DOI: 10.1002/embr.201338390. View

10.

La X, Zhang L, Li H, Li Z, Song G, Yang P . Ajuba receptor mediates the internalization of tumor-secreted GRP78 into macrophages through different endocytosis pathways. Oncotarget. 2018; 9(21):15464-15479. PMC: 5884641. DOI: 10.18632/oncotarget.24090. View

11.

Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H . Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One. 2013; 8(10):e77070. PMC: 3795022. DOI: 10.1371/journal.pone.0077070. View

12.

Ried K, Toben C, Fakler P . Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013; 71(5):282-99. DOI: 10.1111/nure.12012. View

13.

Han P, Li W, Lin C, Yang J, Shang C, Nuernberg S . A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 2014; 514(7520):102-106. PMC: 4184960. DOI: 10.1038/nature13596. View

14.

Lee Y, Seo J, Yoon T, Seo I, Im D, Lee J . Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial. J Hum Nutr Diet. 2016; 29(4):477-86. DOI: 10.1111/jhn.12349. View

15.

Hu C, Yang J, He Q, Luo Y, Chen Z, Yang L . CysLTR1 Blockage Ameliorates Liver Injury Caused by Aluminum-Overload via PI3K/AKT/mTOR-Mediated Autophagy Activation in Vivo and in Vitro. Mol Pharm. 2018; 15(5):1996-2006. DOI: 10.1021/acs.molpharmaceut.8b00121. View

16.

Li Q, Peng H, Fan H, Zou X, Liu Q, Zhang Y . The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction. Cell Death Differ. 2015; 23(1):158-68. PMC: 4815986. DOI: 10.1038/cdd.2015.83. View

17.

Scheving L, Zhang X, Garcia O, Wang R, Stevenson M, Threadgill D . Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice. Am J Physiol Gastrointest Liver Physiol. 2014; 306(5):G370-81. PMC: 3949019. DOI: 10.1152/ajpgi.00116.2013. View

18.

Deshmukh H, Colhoun H, Johnson T, McKeigue P, Betteridge D, Durrington P . Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a). J Lipid Res. 2012; 53(5):1000-1011. PMC: 3329377. DOI: 10.1194/jlr.P021113. View

19.

Terrell A, Crisostomo P, Wairiuko G, Wang M, Morrell E, Meldrum D . Jak/STAT/SOCS signaling circuits and associated cytokine-mediated inflammation and hypertrophy in the heart. Shock. 2006; 26(3):226-34. DOI: 10.1097/01.shk.0000226341.32786.b9. View

20.

Lee J . Epigenetic regulation by long noncoding RNAs. Science. 2012; 338(6113):1435-9. DOI: 10.1126/science.1231776. View