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LncRNA RNCR3 promotes endothelial cell proliferation and inflammatory cytokine secretion via regulating miR-185-5p/cyclin D2 axis

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Abstract

Endothelial cell is one critical structure of blood vessels, and irregular migration and proliferation of endothelial cell might cause progression of several vascular diseases such as atherosclerosis and restenosis. We showed that TNF-α, PDGF-bb, and IL-1β promote RNCR3 expression in a dose-dependent manner inhuman endothelial cell. RNCR3 level is higher in serum of atherosclerosis patients compared with those in control volunteers. Overexpression of RNCR3 promotes cell proliferation and three inflammatory cytokine secretion including IL-6, IL-1β, and TNF-α in endothelial cell. We illustrated that overexpression of RNCR3 inhibits miR-185-5p expression in endothelial cell. Furthermore, we indicated that miR-185-5p level is lower in the serum of patients with atherosclerosis compared with those in control volunteers. There is a negative correlation between miR-185-5p and RNCR3 expression in serum of patients with atherosclerosis. Using Targetscan, it predicted that miR-185-5p may bind to cyclin D2 and miR-185-5p is one potential target of miR-185-5p. Luciferase reporter data indicated that miR-185-5p suppresses luciferase value of wild-type cyclin D2 while it has no influence of cyclin D2 mutant. Overexpression of RNCR3 enhances cyclin D2 expression in endothelial cell. Moreover, RNCR3 induces cell growth and enhances inflammatory cytokine secretion through modulating cyclin D2 expression in endothelial cell. These results suggested that RNCR3 may serve as one new target for the treatment of atherosclerosis.

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References

  • Ahmed A et al (2018) Long noncoding RNA (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells. Proc Natl Acad Sci USA 115(37):E8660–E8667. https://doi.org/10.1073/pnas.1803725115

    Article  CAS  Google Scholar 

  • Ba ZW, Gu LL, Hao SN, Wang XF, Cheng ZP, Nie GC (2018) Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR-181a. Cell Prolif 51:ARTN e12409. https://doi.org/10.1111/cpr.12409

    Article  CAS  Google Scholar 

  • Bai S et al (2020) Orai-IGFBP3 signaling complex regulates high-glucose exposure-induced increased proliferation, permeability, and migration of human coronary artery endothelial cells. BMJ Open Diabetes Res Care 8. https://doi.org/10.1136/bmjdrc-2020-001400

  • Bian W et al (2020) Downregulation of LncRNA NORAD promotes Ox-LDL-induced vascular endothelial cell injury and atherosclerosis. Aging 12. https://doi.org/10.18632/aging.103034

  • Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6:e1001233. https://doi.org/10.1371/journal.pgen.1001233

    Article  CAS  Google Scholar 

  • Cao C et al (2019) LINC01303 functions as a competing endogenous RNA to regulate EZH2 expression by sponging miR-101-3p in gastric cancer. J Cell Mol Med. https://doi.org/10.1111/jcmm.14593

  • Chen C, Cheng GQ, Yang XN, Li CS, Shi R, Zhao NN (2016) Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a. Am J Transl Res 8:2981–2991

    CAS  Google Scholar 

  • Chen Q, Huang X, Li R (2018) lncRNA MALAT1/miR-205-5p axis regulates MPP-induced cell apoptosis in MN9D cells by directly targeting LRRK2. Am J Transl Res 10:563–572

    CAS  Google Scholar 

  • Chung D, Wu Y, Yang M, Chan K, Lee H, Wang C (2020) Nelumbo nucifera leaf polyphenol extract and gallic acid inhibit TNF-α-induced vascular smooth muscle cell proliferation and migration involving the regulation of miR-21, miR-143 and miR-145. Food Funct 11:8602–8611. https://doi.org/10.1039/d0fo02135k

    Article  CAS  Google Scholar 

  • Cui C et al (2019) lncRNA 430945 promotes the proliferation and migration of vascular smooth muscle cells via the ROR2/RhoA signaling pathway in atherosclerosis. Mol Med Rep 19:4663–4672

    CAS  Google Scholar 

  • Geng ZH (2016) MiR-129-5p-mediated Beclin-1 suppression inhibits endothelial cell autophagy in atherosclerosis. J Am Coll Cardiol 68:C37–C37

    Google Scholar 

  • Holdt LM et al (2010) ANRIL expression and atherosclerosis severity at chromosome 9p21. Eur Heart J 31:901–901

    Google Scholar 

  • Khalili HR, Adeli Behrooz HR, Rashidi Nooshabadi MR, Geravandi S, Mohammadi MJ, Foruozandeh H (2020 Apr 2) Evaluation of potential anti-fibrotic effect of oleuropein on bleomycin-induced pulmonary fibrosis in rat. Toxin Rev 39(2):188–196

    Article  Google Scholar 

  • Li Y et al (2018) Long non-coding RNA FAL1 functions as a ceRNA to antagonize the effect of miR-637 on the down-regulation of AKT1 in Hirschsprung's disease. Cell Prolif 51:ARTN e12489. https://doi.org/10.1111/cpr.12489

    Article  CAS  Google Scholar 

  • Li Z et al (2019) Emerging roles of long non-coding RNAs in neuropathic pain. Cell Prolif 52:ARTN e12528. https://doi.org/10.1111/cpr.12528

    Article  Google Scholar 

  • Li Z, Li X, Shen J, Zhang L, Chan MTV, Wu WKK (2020) Emerging roles of non-coding RNAs in scoliosis. Cell Prolif 53:e12736. https://doi.org/10.1111/cpr.12736

    Article  Google Scholar 

  • Liang Z, Cao Y, Wei M, Xue J, Dong J (2018) Long noncoding RNA-RNCR3 overexpression deleteriously affects the growth of glioblastoma cells through miR-185-5p/Krüppel-like factor 16 axis. J Cell Biochem 119:9081–9089. https://doi.org/10.1002/jcb.27167

    Article  CAS  Google Scholar 

  • Ma X et al (2020) ApoeFunctional nano-vector boost anti-atherosclerosis efficacy of berberine in mice. Acta Pharm Sin B 10:1769–1783. https://doi.org/10.1016/j.apsb.2020.03.005

    Article  CAS  Google Scholar 

  • Rhee SW, Stimers JR, Wang W, Pang L (2009) Vascular smooth muscle-specific knockdown of the noncardiac form of the L-type calcium channel by microRNA-based short hairpin RNA as a potential antihypertensive therapy. J Pharmacol Exp Ther 329:775–782. https://doi.org/10.1124/jpet.108.148866

    Article  CAS  Google Scholar 

  • Shan R, Liu N, Yan Y, Liu B (2020) Apoptosis, autophagy and atherosclerosis: relationships and the role of Hsp27. Pharmacol Res:105169. https://doi.org/10.1016/j.phrs.2020.105169

  • Shang W, Tang Z, Gao Y, Qi H, Su X, Zhang Y, Yang R (2017) LncRNA RNCR3 promotes Chop expression by sponging miR-185-5p during MDSC differentiation. Oncotarget 8:111754–111769. https://doi.org/10.18632/oncotarget.22906

    Article  Google Scholar 

  • Simion V et al (2020) LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling. JCI insight. https://doi.org/10.1172/jci.insight.140627

  • Sun B, Meng M, Wei J, Wang S (2020a) Long noncoding RNA PVT1 contributes to vascular endothelial cell proliferation via inhibition of miR-190a-5p in diagnostic biomarker evaluation of chronic heart failure. Exp Ther Med 19:3348–3354. https://doi.org/10.3892/etm.2020.8599

    Article  CAS  Google Scholar 

  • Sun L-L, Lei F-R, Jiang X-D, Xiao-Long D, Xiao L, Li W-D, Li X-Q (2020b) LncRNA GUSBP5-AS promotes EPC migration and angiogenesis and deep vein thrombosis resolution by regulating FGF2 and MMP2/9 through the miR-223-3p/FOXO1/Akt pathway. Aging 12:4506–4526. https://doi.org/10.18632/aging.102904

    Article  CAS  Google Scholar 

  • Tian C, Deng Y, Jin Y, Shi S, Bi H (2018) Long non-coding RNA RNCR3 promotes prostate cancer progression through targeting miR-185-5p. Am J Transl Res 10:1562–1570

    CAS  Google Scholar 

  • Wang X, Li D, Chen H, Wei X, Xu X (2019) Expression of long noncoding RNA LIPCAR promotes cell proliferation, cell migration, and change in phenotype of vascular smooth muscle cells Medical science monitor. Med Sci Mon Int Med J Exp Clin Res 25:7645–7651

    CAS  Google Scholar 

  • Wu ZH, He YY, Li DL, Fang X, Shang T, Zhang HK, Zheng XT (2017) Long noncoding RNA MEG3 suppressed endothelial cell proliferation and migration through regulating miR-21. Am J Transl Res 9:3326–3335

    CAS  Google Scholar 

  • Xu Z et al (2015) MiR-135b-5p and MiR-499a-3p promote cell proliferation and migration in atherosclerosis by directly targeting MEF2C. Sci Rep 5:12276. https://doi.org/10.1038/srep12276

    Article  CAS  Google Scholar 

  • Xu RD, Feng F, Yu XS, Liu ZD, Lao LF (2018) LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma. Cell Prolif 51:ARTN e12515. https://doi.org/10.1111/cpr.12515

    Article  CAS  Google Scholar 

  • Xu G et al (2020) RUNX1-activated upregulation of lncRNA RNCR3 promotes cell proliferation, invasion, and suppresses apoptosis in colorectal cancer via miR-1301-3p/AKT1 axis in vitro and in vivo. Clin Transl Oncol. https://doi.org/10.1007/s12094-020-02335-5

  • Yang C, Wu K, Wang S, Wei G (2018) Long non-coding RNA XIST promotes osteosarcoma progression by targeting YAP via miR-195-5p. J Cell Biochem 119(7):5646–5656. https://doi.org/10.1002/jcb.26743

    Article  CAS  Google Scholar 

  • Zhang CF, Kang K, Li XM, Xie BD (2015a) MicroRNA-136 promotes vascular muscle cell proliferation through the ERK1/2 pathway by targeting PPP2R2A in atherosclerosis. Curr Vasc Pharmacol 13:405–412

    Article  CAS  Google Scholar 

  • Zhang Y et al (2015b) MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis. Sci Rep 5:9401. https://doi.org/10.1038/srep09401

    Article  CAS  Google Scholar 

  • Zhang SL, Dong XX, Ji TY, Chen GX, Shan L (2017) Long non-coding RNA UCA1 promotes cell progression by acting as a competing endogenous RNA of ATF2 in prostate cancer. Am J Transl Res 9:366–375

    CAS  Google Scholar 

  • Zhang C, Yang H, Li Y, Huo P, Ma P (2020a) LNCRNA OIP5-AS1 regulates oxidative low-density lipoprotein-mediated endothelial cell injury via miR-320a/LOX1 axis. Mol Cell Biochem 467:15–25. https://doi.org/10.1007/s11010-020-03688-9

    Article  CAS  Google Scholar 

  • Zhang R, Huang X-Q, Jiang Y-Y, Li N, Wang J, Chen S-Y (2020b) LncRNA TUG1 regulates autophagy-mediated endothelial-mesenchymal transition of liver sinusoidal endothelial cells by sponging miR-142-3p. Am J Transl Res 12:758–772

    CAS  Google Scholar 

  • Zhao J, Gao Z, Zhang C, Wu H, Gu R, Jiang R (2018) Long non-coding RNA ASBEL promotes osteosarcoma cell proliferation, migration and invasion by regulating microRNA-21. J Cell Biochem 119(8):6461–6469. https://doi.org/10.1002/jcb.26671

    Article  CAS  Google Scholar 

  • Zheng JL, Yi D, Liu Y, Wang MQ, Zhu YL, Shi HZ (2017) Long nonding RNA UCA1 regulates neural stem cell differentiation by controlling miR-1/Hes1 expression. Am J Transl Res 9:3696–3704

    CAS  Google Scholar 

  • Zheng J, Zhuo Y-Y, Zhang C, Tang G-Y, Gu X-Y, Wang F (2020) LncRNA TTTY15 regulates hypoxia-induced vascular endothelial cell injury via targeting miR-186-5p in cardiovascular disease. Eur Rev Med Pharmacol Sci 24:3293–3301. https://doi.org/10.26355/eurrev_202003_20697

    Article  CAS  Google Scholar 

  • Zhu SB, Fu W, Zhang LY, Fu K, Hu JH, Jia W, Liu GC (2018) LINC00473 antagonizes the tumour suppressor miR-195 to mediate the pathogenesis of Wilms tumour via IKK. Cell Prolif 51:ARTN e12416. https://doi.org/10.1111/cpr.12416

    Article  CAS  Google Scholar 

  • Zou YF et al (2018) Long non-coding PANDAR as a novel biomarker in human cancer: a systematic review. Cell Prolif 51:ARTN e12422. https://doi.org/10.1111/cpr.12422

    Article  CAS  Google Scholar 

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Funding

This study was supported by Quanzhou High-level Talents Innovation and Entrepreneurship Project (2018C059R), Science and Technology Project of Quanzhou Fujian Provincial (No. 2018Z095, 2016Z060), and Fujian Natural Science Foundation Project (2019J01600).

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Authors and Affiliations

  1. Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China

    Quanlong Hong & Wenli Huang

  2. Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China

    Lin Ling, Yilan Liu, Yafen Zhuo, Zhenzhen Hong & Yi Zhang

  3. Department of Cardiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China

    Bing Wu

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  1. Quanlong Hong
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  2. Lin Ling
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  4. Yilan Liu
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  5. Yafen Zhuo
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  6. Zhenzhen Hong
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  7. Bing Wu
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Contributions

Quanlong Hong, Lin Ling, Wenli Huang, Yilan Liu, Yafen Zhuo, Zhenzhen Hong, Bing Wu3, and Yi Zhang designed and conceived the experiments, performed the data analysis, drafted the original manuscript, and revised manuscript.

Corresponding authors

Correspondence to Bing Wu or Yi Zhang.

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Ethical approval

All healthy volunteers and patients signed informed consent and this study was approved with clinical Ethics Committee of Quanzhou First Hospital Affiliated to Fujian Medical University (NO. 2018062).

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The authors declare that they have no conflict of interest.

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Responsible Editor: Mohamed M. Abdel-Daim

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Quanlong Hong and Lin Ling are co-first authors.

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Hong, Q., Ling, L., Huang, W. et al. LncRNA RNCR3 promotes endothelial cell proliferation and inflammatory cytokine secretion via regulating miR-185-5p/cyclin D2 axis. Environ Sci Pollut Res 28, 27025–27032 (2021). https://doi.org/10.1007/s11356-020-12117-9

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  • DOI: https://doi.org/10.1007/s11356-020-12117-9

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