LINC00926 is involved in hypoxia-induced vascular endothelial cell dysfunction via miR-3194-5p regulating JAK1/STAT3 signaling pathway

Submitted: 12 August 2022
Accepted: 29 December 2022
Published: 16 January 2023
Abstract Views: 1022
PDF: 565
HTML: 28
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Vascular endothelial cell (VEC) dysfunction is associated with the development of coronary heart disease (CHD). Long intergenic non-protein coding RNA 926 (LINC00926), a kind of long noncoding RNA (lncRNA), has been found to be abnormally expressed in CHD patients. However, the biological role of LINC00926 has not been reported. In our research, we intended to explore the regulatory mechanism of LINC00926 in hypoxia-exposed HUVEC cells (HUVECs). In our in vitro study, HUVECs were exposed under hypoxic conditions (5% O2) for 24 h. RT-qPCR and Western blotting assay were used to detect the mRNA and protein levels. CCK-8 assay, flow cytometry, transwell assay and in vitro angiogenesis assay were performed to measure cell proliferation, apoptosis, migration and tube formation, respectively. Bioinformatics analysis was applied to predict the target of LINC00926 and miR-3194-5p, which was verified by dual-luciferase reporter assays. The results showed that LINC00926 was highly expressed in CHD patients and hypoxia-exposed HUVECs. LINC00926 overexpression suppressed cell proliferation, migration and tube formation and increased cell apoptosis. MiR-3194-5p was a target of LINC00926 and can target binding to JAK1 3’UTR. LINC00926 could up-regulate JAK1 and p-STAT3 levels via miR-3194-5p. In addition, overexpressed LINC00926 suppressed cell proliferation, migration and tube formation and increased cell apoptosis via miR-3194-5p/JAK1/STAT3 axis. In summary, LINC00926 aggravated endothelial cell dysfunction via miR-3194-5p regulating JAK1/STAT3 signaling pathway in hypoxia-exposed HUVECs.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Xu H, Zhang X, Yu K, Zhang G, Yfei Shi Y, Jiang Y. Analysis on the expression and prognostic value of LncRNA FAF in Patients with coronary heart disease. Biomed Res Int 2020;2020:9471329. DOI: https://doi.org/10.1155/2020/9471329
Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016;118:620-36. DOI: https://doi.org/10.1161/CIRCRESAHA.115.306301
Chamorro-Jorganes A, Araldi E, Suárez Y. MicroRNAs as pharmacological targets in endothelial cell function and dysfunction. Pharmacol Res 2013;75:15-27. DOI: https://doi.org/10.1016/j.phrs.2013.04.002
Archer K, Broskova Z, Bayoumi AS, Teoh JP, Davila A, Tang Y, et al. Long non-coding RNAs as master regulators in cardiovascular diseases. Int J Mol Sci 2015;16:23651-67. DOI: https://doi.org/10.3390/ijms161023651
Li H, Zhu H, Ge J. Long noncoding RNA: Recent updates in atherosclerosis. Int J Mol Sci 2016;12:898-910. DOI: https://doi.org/10.7150/ijbs.14430
Zheng J, Zhuo YY, Zhang C, G-Y Tang, Gu X-Y, Wang F. LncRNA TTTY15 regulates hypoxia-induced vascular endothelial cell injury via targeting miR-186-5p in cardiovascular disease. Eur Rev Med Pharmacol Sci 2020;24:3293-301.
Guo FX, Wu Q, Li P, Zheng L, Ye S, Daiet X-Y, al. The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling. Cell Death Differ 2019;26:1670-87. DOI: https://doi.org/10.1038/s41418-018-0235-z
Liao J, Wang J, Liu Y, Li J, Duan L. Transcriptome sequencing of lncRNA, miRNA, mRNA and interaction network constructing in coronary heart disease. BMC Med Genomics 2019;12:124. DOI: https://doi.org/10.1186/s12920-019-0570-z
Huang Y. The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases. J Cell Mol Med 2018;22:5768-75. DOI: https://doi.org/10.1111/jcmm.13866
Chen Q, Lv J, Yang W, et al. Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis. Theranostics 2019;9:6424-62. DOI: https://doi.org/10.7150/thno.35528
Hu Y, Xu R, He Y, Zhao Z, Mao X, Linet L, et al. Downregulation of microRNA‑106a‑5p alleviates ox‑LDL‑mediated endothelial cell injury by targeting STAT3. Mol Med Rep 2020;22:783-91. DOI: https://doi.org/10.3892/mmr.2020.11147
Bonnin DA, Havrda MC, Lee MC, Liu H, Zhang Z, Nguyen LN, et al. Secretion-mediated STAT3 activation promotes self-renewal of glioma stem-like cells during hypoxia. Oncogene 2018;37:1107-18. DOI: https://doi.org/10.1038/onc.2017.404
Kurdi M, Sivakumaran V, Duhé RJ, Aon MA, Paolocci N, Booz GW. Depletion of cellular glutathione modulates LIF-induced JAK1-STAT3 signaling in cardiac myocytes. Int J Biochem Cell Biol 2012;44:2106-15. DOI: https://doi.org/10.1016/j.biocel.2012.08.016
Zhai S, Zhang XF, Lu F, Chen WG, He X, Zhanget C-F, al. Chinese medicine GeGen-DanShen extract protects from myocardial ischemic injury through promoting angiogenesis via up-regulation of VEGF/VEGFR2 signaling pathway. J Ethnopharmacol 2021;267:113475. DOI: https://doi.org/10.1016/j.jep.2020.113475
Yu F, Zhang Y, Wang Z, et al. Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3. Theranostics 2021;11:5404-17. DOI: https://doi.org/10.7150/thno.48389
Zhang Q, Liu J, Duan H, Li R, Peng W, Wu C. Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. J Adv Res 2021;34:43-63. DOI: https://doi.org/10.1016/j.jare.2021.06.023
Hosen MR, Nickenig G, Jansen F. Coronary artery disease ameliorates extracellular vesicle lncRNA PUNISHER regulates angiogenic response andendothelial cells function via NFkB-dependent mechanism. Eur Heart J 2022;43:ehac544.2935. DOI: https://doi.org/10.1093/eurheartj/ehac544.2935
Liu X, Li S, Yang Y, Sun Y, Yang Q, Gu N, et al. The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-βR1 signalling pathway. J Cell Physiol 2021;236:2058-69. DOI: https://doi.org/10.1002/jcp.29993
Mao J, Zhou Y, Lu L, Zhang P, Ren R, Wang Y, et al. Identifying a Serum exosomal-associated lncRNA/circRNA-miRNA-mRNA network in coronary heart disease. Cardiol Res Pract 2021;2021:6682183. DOI: https://doi.org/10.21203/rs.3.rs-131078/v2
Lin L, Bao J. Long non-coding RNA THRIL is upregulated in coronary heart disease and binds to microRNA-424 to upregulate TXNIP in mice. Microvasc Res 2021;138:104215. DOI: https://doi.org/10.1016/j.mvr.2021.104215
Huang YC, Tsai TC, Chang CH, Chang K-T, Ko P-H, Lai L-C. Indoxyl Sulfate elevated Lnc-SLC15A1-1 upregulating CXCL10/CXCL8 expression in high-glucose endothelial cells by sponging microRNAs. Toxins (Basel) 2021;13:873. DOI: https://doi.org/10.3390/toxins13120873
Kim M, Morales LD, Jang IS, Cho Y-Y, Kim DJ. Protein tyrosine phosphatases as potential regulators of STAT3 signaling. Int J Mol Sci 2018;19:2708. DOI: https://doi.org/10.3390/ijms19092708
Bromberg JF. Activation of STAT proteins and growth control. Bioessays 2001;23:161-9. DOI: https://doi.org/10.1002/1521-1878(200102)23:2<161::AID-BIES1023>3.0.CO;2-0
Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol 2007;178:2623-9. DOI: https://doi.org/10.4049/jimmunol.178.5.2623
Ni CW, Hsieh HJ, Chao YJ, Wang DL. Interleukin-6-induced JAK2/STAT3 signaling pathway in endothelial cells is suppressed by hemodynamic flow. Am J Physiol Cell Physiol 2004;287:C771-80. DOI: https://doi.org/10.1152/ajpcell.00532.2003

Ethics Approval

This study was approved by the Ethics Committee of Jilin Medical University

How to Cite

Jiang, Y., Xu, C.- hui ., Zhao, Y. ., Ji, . Y.- han ., Wang, X.- tao ., & Liu, Y. . (2023). LINC00926 is involved in hypoxia-induced vascular endothelial cell dysfunction <em>via</em> miR-3194-5p regulating JAK1/STAT3 signaling pathway. European Journal of Histochemistry, 67(1). https://doi.org/10.4081/ejh.2023.3526

Similar Articles

1 2 3 4 5 6 7 8 > >> 

You may also start an advanced similarity search for this article.

Publication Facts

Metric
This article
Other articles
Peer reviewers 
2
2.4

Reviewer profiles  N/A

Author statements

Author statements
This article
Other articles
Data availability 
N/A
16%
External funding 
N/A
32%
Competing interests 
N/A
11%
Metric
This journal
Other journals
Articles accepted 
57%
33%
Days to publication 
156
145

Indexed in

Editor & editorial board
profiles
Academic society 
N/A