Inhibition of lncRNA DANCR Prevents Heart Failure by Ameliorating Cardiac Hypertrophy and Fibrosis Via Regulation of the miR-758-3p/PRG4/Smad Axis

Journal of Cardiovascular Translational Research - Tập 16 - Trang 1357-1372 - 2023
Qianwen Huang1, Qian Huang2
1Department of Cardiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
2Teaching and Research Section of Physiology, Basic Medicine Department, Quanzhou Medical College, Quanzhou, China

Tóm tắt

The current work was developed to explore the functions and possible mechanism of PRG4 in cardiac hypertrophy and heart failure. Ang II-stimulated H9c2 cells and AC16 cells were used as in vitro cell models. The binding relation between genes in cells was explored using luciferase reporter assays and RNA immunoprecipitation assay. The cardiac functions of rats received transverse-ascending aortic constriction (TAC) surgery and adeno-associated virus (AAV) injection were examined with echocardiography. The myocardial histological changes were observed using H&E, wheat germ agglutinin, and sirius red staining. It was discovered that PRG4 silencing attenuated cell hypertrophy and fibrosis and inactivated the Smad pathway under Ang II treatment. PRG4 was targeted by miR-758-3p, and miR-758-3p interacted with long noncoding RNA DANCR. DANCR silencing inhibited cardiac dysfunction, fibrosis, and TGFβ1/Smad pathway. In addition, DANCR was highly expressed in myocardial extracellular vesicles. Overall, DANCR depletion prevents heart failure by inhibiting cardiac hypertrophy and fibrosis via the miR-758-3p/PRG4/Smad pathway.

Tài liệu tham khảo

Vaidya, Y., S. Riaz, and A.S. Dhamoon, Left ventricular assist devices, in StatPearls. 2023, StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.: Treasure Island (FL) ineligible companies. Disclosure: Sana Riaz declares no relevant financial relationships with ineligible companies. Disclosure: Amit Dhamoon declares no relevant financial relationships with ineligible companies. Meijers WC, de Boer RA. Common risk factors for heart failure and cancer. Cardiovasc Res. 2019;115(5):844–53. Funamoto M, et al. Roles of histone acetylation sites in cardiac hypertrophy and heart failure. Front Cardiovasc Med. 2023;10:1133611. Mouton AJ, et al. Interaction of obesity and hypertension on cardiac metabolic remodeling and survival following myocardial infarction. J Am Heart Assoc. 2021;10(6):e018212. Funamoto, M., et al., Pyrazole-curcumin suppresses cardiomyocyte hypertrophy by disrupting the CDK9/CyclinT1 complex. Pharmaceutics, 2022; 14(6). Zhang Q, et al. Long noncoding RNA MAGI1-IT1 regulates cardiac hypertrophy by modulating miR-302e/DKK1/Wnt/beta-catenin signaling pathway. J Cell Physiol. 2020;235(1):245–53. Zhang J, et al. Neohesperidin inhibits cardiac remodeling induced by Ang II in vivo and in vitro. Biomed Pharmacother. 2020;129:110364. Chen X, et al. Dapagliflozin attenuates myocardial fibrosis by inhibiting the TGF-β1/Smad signaling pathway in a normoglycemic rabbit model of chronic heart failure. Front Pharmacol. 2022;13:873108. Venugopal, H., et al., Properties and functions of fibroblasts and myofibroblasts in myocardial infarction. Cells, 2022; 11(9). Huang S, et al. Distinct roles of myofibroblast-specific Smad2 and Smad3 signaling in repair and remodeling of the infarcted heart. J Mol Cell Cardiol. 2019;132:84–97. Zheng QN, et al. QiShenYiQi Pills(®) ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway. Pharmacol Res. 2019;146:104272. Solakyildirim K, et al. Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis. Glycobiology. 2021;31(11):1582–95. Seime, T., et al., Proteoglycan 4 modulates osteogenic smooth muscle cell differentiation during vascular remodeling and intimal calcification. Cells, 2021; 10(6). Jiang XY, Ning QL. Expression profiling of long noncoding RNAs and the dynamic changes of lncRNA-NR024118 and Cdkn1c in angiotensin II-treated cardiac fibroblasts. Int J Clin Exp Pathol. 2014;7(4):1325–36. Artiach, G., et al., Proteoglycan 4 is increased in human calcified aortic valves and enhances valvular interstitial cell calcification. Cells, 2020; 9(3). Park DSJ, et al. Human pericardial proteoglycan 4 (lubricin): implications for postcardiotomy intrathoracic adhesion formation. J Thorac Cardiovasc Surg. 2018;156(4):1598-1608.e1. Sawada K, et al. Antiseptic solutions modulate the paracrine-like activity of bone chips: differential impact of chlorhexidine and sodium hypochlorite. J Clin Periodontol. 2015;42(9):883–91. Schmidt TA, et al. Differential regulation of proteoglycan 4 metabolism in cartilage by IL-1alpha, IGF-I, and TGF-beta1. Osteoarthr Cartil. 2008;16(1):90–7. Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016;17(5):272–83. Li Y, et al. Noncoding RNAs in cardiac hypertrophy. J Cardiovasc Transl Res. 2018;11(6):439–49. Zhu L, et al. Non-coding RNAs: the key detectors and regulators in cardiovascular disease. Genomics. 2021;113(1 Pt 2):1233–46. Yang L, et al. Ablation of lncRNA Miat attenuates pathological hypertrophy and heart failure. Theranostics. 2021;11(16):7995–8007. Cai B, et al. Long noncoding RNA-DACH1 (Dachshund Homolog 1) regulates cardiac function by inhibiting SERCA2a (sarcoplasmic reticulum calcium ATPase 2a). Hypertension. 2019;74(4):833–42. Zhang M, et al. LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s. Aging (Albany NY). 2020;12(2):1778–91. Zhang Z, et al. Emerging role of lncRNA DANCR in progenitor cells: beyond cancer. Eur Rev Med Pharmacol Sci. 2021;25(3):1399–409. Li J, et al. Mir-30d regulates cardiac remodeling by intracellular and paracrine signaling. Circ Res. 2021;128(1):e1–23. McGeary, S.E., et al., The biochemical basis of microRNA targeting efficacy. Science, 2019; 366(6472). Li JH, et al. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42(Database issue):D92-7. Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127-d131. Xiao L, et al. The long noncoding RNA XIST regulates cardiac hypertrophy by targeting miR-101. J Cell Physiol. 2019;234(8):13680–92. Wei Q, et al. Long noncoding RNA NEAT1 promotes myocardiocyte apoptosis and suppresses proliferation through regulation of miR-129-5p. J Cardiovasc Pharmacol. 2019;74(6):535–41. Forrester SJ, et al. Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology. Physiol Rev. 2018;98(3):1627–738. Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292(1):C82-97. Ye S, et al. Celastrol attenuates angiotensin II-induced cardiac remodeling by targeting STAT3. Circ Res. 2020;126(8):1007–23. Zhang M, et al. Contractile function during angiotensin-II activation: increased Nox2 activity modulates cardiac calcium handling via phospholamban phosphorylation. J Am Coll Cardiol. 2015;66(3):261–72. Mann S, et al. Effects of acute angiotensin II on ischemia reperfusion injury following myocardial infarction. J Renin Angiotensin Aldosterone Syst. 2015;16(1):13–22. Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy. Lancet. 2017;389(10075):1253–67. Song, C., et al., Inhibition of lncRNA Gm15834 attenuates autophagy-mediated myocardial hypertrophy via the miR-30b-3p/ULK1 axis in mice. Mol Ther, 2020. Fernández-Ruiz I. H19 in cardiac hypertrophy. Nat Rev Cardiol. 2020;17(10):612. Wang D, et al. Up-regulation of SNHG16 induced by CTCF accelerates cardiac hypertrophy by targeting miR-182-5p/IGF1 axis. Cell Biol Int. 2020;44(7):1426–35. Zhang XH, et al. LncRNA DANCR-miR-758-3p-PAX6 molecular network regulates apoptosis and autophagy of breast cancer cells. Cancer Manag Res. 2020;12:4073–84. Wang S, Jiang M. The long non-coding RNA-DANCR exerts oncogenic functions in non-small cell lung cancer via miR-758-3p. Biomed Pharmacother. 2018;103:94–100. Yao Y, et al. Let-7f regulates the hypoxic response in cerebral ischemia by targeting NDRG3. Neurochem Res. 2017;42(2):446–54. Wang L, et al. Inhibitory effects of PRG4 on migration and proliferation of human venous cells. J Surg Res. 2020;253:53–62.