Calcific aortic valve disease (CAVD) is featured by thickening and calcification of the aortic valve. Osteoblast differentiation is a crucial step in valve calcification. Long non-coding RNAs (LncRNAs) participate in the osteogenic differentiation of mesenchymal cells. However, the character of lncRNA FGD5 antisense RNA 1 (FGD5-AS1) in CAVD is uncertain. After collection of human aortic valve tissue samples, detection of FGD5-AS1, microRNA (miR)-497-5p and Baculovirus inhibitor 5 (BIRC5) was conducted. Valve mesenchymal cells were isolated from CAVD patients and induced to differentiate to osteoblasts, and transfected with FGD5-AS1, miR-497-5p and BIRC5 plasmids. Detection of the alkaline phosphatase activity was after osteogenic induction of human aortic valve interstitial cells (hAVICs); Detection of the degree of calcium nodules and osteoblast differentiation markers (RUNX2 and OPN) was conducted. After establishment of a mouse model of CAVD, detection of the thickness of aortic valve leaflets, and the degree of calcification of the valve leaflets, and evaluation of echocardiographic parameters were implemented. Experimental data manifested in CAVD patients, lncRNAFGD5-AS1 and BIRC5 were reduced, but miR-497-5p was elevated; Enhancing lncRNA FGD5-AS1 or repressing miR-497-5p mitigated CAVD by restraining osteogenic differentiation; LncRNA FGD5-AS1 sponged miR-497-5p to target BIRC5; Repressive BIRC5 turned around the therapeutic action of elevated FGD5-AS1 or depressed miR-497-5p on hAVICs; Enhancive FGD5-AS1 in vivo was available to reduce ApoE-/- mouse CAVD induced via high cholesterol diet. All in all, lncRNAFGD5-AS1 targets BIRC5 via miR-497-5p to alleviate CAVD.
MaXiaochun, ZhaoDiming, YuanPeidonget al.Endothelial-to-Mesenchymal Transition in Calcific Aortic Valve Disease. Journal of Acta Cardiol Sin. 2020;36:183–194.
3.
DahalSudip, HuangPeter, MurrayBruce Tet al.Endothelial to mesenchymal transformation is induced by altered extracellular matrix in aortic valve endothelial cells. Journal of J Biomed Mater Res A. 2017;105:2729–2741.
4.
DimmelerS, HaendelerJ, GalleJet al.Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the ‘response to injury’ hypothesis. Journal of Circulation. 1997;95:1760–3.
5.
ZhangPu, WangWeiping, LiMeilan, Role and mechanism of circular RNA circ_0050486 in regulating oxidized low-density lipoprotein-induced injury in endothelial cells. Journal of Clin Hemorheol Microcirc. 2022;82:107–124.
6.
ZhuLingfeng, ZhaoPing, MengXianweiet al.Circ_0091822 aggravates ox-LDL-induced endothelial cell injury through targeting the miR-661/RAB22A axis. Journal of Clin Hemorheol Microcirc. 2023;83:47–59.
7.
LiuFang, GaoBo, WangYu, CircIRAK1 aggravates ox-LDL-induced endothelial cell injury in atherosclerosis via TRIM14 upregulation by binding to miR-330-5p1. Journal of Clin Hemorheol Microcirc, 2022, undefined: undefined.
8.
WeiWenbo, TangMin, WangQiet al.Circ_HECW2 regulates ox-LDL-induced dysfunction of cardiovascular endothelial cells by miR-942-5p/TLR4 axis. Journal of Clin Hemorheol Microcirc, 2022, undefined: undefined.
9.
JiaoW, ZhangD, WangD, XuR, TangL, ZhaoM, XuR. MicroRNA-638 inhibits human aortic valve interstitial cell calcification by targeting Sp7. Journal of Cellular and Molecular Medicine. 2019;23(8):5292–5302.
10.
YuC, WuD, ZhaoC, WuC. CircRNA TGFBR2/MiR-25-3p/TWIST1 axis regulates osteoblast differentiation of human aortic valve interstitial cells. Journal of Bone and Mineral Metabolism. 2021;39(3):360–371.
11.
ZhuE, LiuZ, HeW, DengB, ShuX, HeZ, WuX, KeX, NieR. CC chemokine receptor 2 functions in osteoblastic transformation of valvular interstitial cells. Life Sciences. 2019;228:72–84.
12.
HutchesonJ, AikawaE, MerrymanW. Potential drug targets for calcific aortic valve disease. Nature reviews Cardiology. 2014;11(4):218–231.
13.
WangY, ZhuP, WangJ, ZhuX, LuoJ, MengS, WuJ, YeB, HeL, DuY, et al.Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling. Journal of Hepatology. 2018;69(4):861–872.
14.
HadjiF, BoulangerM, GuayS, GaudreaultN, AmellahS, MkannezG, BoucharebR, MarchandJ, NsaibiaM, Guauque-OlarteS, et al.Altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease Promotes Mineralization by Silencing NOTCH1. Circulation. 2016;134(23):1848–1862.
15.
ZhangX, GaoY, ZhangX, ZhangX, XiangY, FuQ, WangB, XuZ. FGD5-AS1 Is a Hub lncRNA ceRNA in Hearts With Tetralogy of Fallot Which Regulates Congenital Heart Disease Genes Transcriptionally and Epigenetically. Frontiers in Cell and Developmental Biology. 2021;9:630634.
16.
ShenL, HuX, ChenT, ShenG, ChengD. Integrated network analysis to explore the key mRNAs and lncRNAs in acute myocardial infarction. Mathematical Biosciences and Engineering: MBE. 2019;16(6):6426–6437.
17.
ChenY, DingJ, ZhouW, ZhangX, SunX, WangX, ZhangC, LiN, ShaoG, HuS, et al.Identification and Functional Prediction of Long Non-Coding RNAs in Dilated Cardiomyopathy by Bioinformatics Analysis. Frontiers in Genetics. 2021;12:648111.
18.
HenshallD, HamerH, PasterkampR, GoldsteinD, KjemsJ, PrehnJ, SchorgeS, LamottkeK, RosenowF. MicroRNAs in epilepsy: pathophysiology and clinical utility. The Lancet Neurology. 2016;15(13):1368–1376.
19.
ZhangF, ChengN, HanY, ZhangC, ZhangH. miRNA Expression Profiling Uncovers a Role of miR-139-5p in Regulating the Calcification of Human Aortic Valve Interstitial Cells. Frontiers in Genetics. 2021;12:722564.
20.
MaJ, LinX, ChenC, LiS, ZhangS, ChenZ, LiD, ZhaoF, YangC, YinC, et al.Circulating miR-181c-5p and miR-497-5p Are Potential Biomarkers for Prognosis and Diagnosis of Osteoporosis. The Journal of Clinical Endocrinology and Metabolism. 2020;105(5).
21.
SathyamurthyI, AlexSJ. Calcific aortic valve disease: is it another face of atherosclerosis?Indian Heart J, 2015;67(5):503–6. doi: 10.1016/j.ihj.2015.07.033.
22.
CaoZY, WangH, ZhuXY. The Role of Serum miR-497 on the Predictive Index of Early Diagnosis and Poor Prognosis of Atherosclerosis Cerebral Infarction. Iran J Public Health. 2021;50(5):927–937. doi: 10.18502/ijph.v50i5.6110.
23.
ZhengD, ZangY, XuH, WangY, CaoX, WangT, PanM, ShiJ, LiX. MicroRNA-214 promotes the calcification of human aortic valve interstitial cells through the acceleration of inflammatory reactions with activated MyD88/NF-κB signaling. Clinical Research in Cardiology: Official Journal of the German Cardiac Society. 2019;108(6):691–702.
24.
ZhengD, WangB, ZhuX, HuJ, SunJ, XuanJ, GeZ. LncRNA OIP5-AS1 inhibits osteoblast differentiation of valve interstitial cells via miR-137/TWIST11 axis. Biochemical and Biophysical Research Communications. 2019;511(4):826–832.
25.
ChenH, LanZ, LiQ, LiY. Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway. Artificial Cells, Nanomedicine, and Biotechnology. 2019;47(1):2098–2106.
26.
DuJ, ZhengR, XiaoF, ZhangS, HeK, ZhangJ, ShaoY. Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of Valve Interstitial Cells via Targeting SMAD7. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2017;44(3):884–896.
NiuHY, QuAN, GuanCY. Suppression of MGAT3 expression and the epithelial-mesenchymal transition of lung cancer cells by miR-188-5p. Biomed J. 2021;44(6):678–685. doi: 10.1016/j.bj.2020.05.010.
31.
FuJ, CaiHM, WuY, FangSY, WangDF. Elevation of FGD5-AS1 contributes to cell progression by improving cisplatin resistance against non-small cell lung cancer cells through regulating miR-140-5p/WEE1 axis. Gene, 755(undefined) 2020;144886. doi: 10.1016/j.gene.2020.144886.
32.
WangS, YangX, XieW, FuS, ChenQ, LiZ, ZhangZ, SunT, GongB, MaM. LncRNA GAPLINC Promotes Renal Cell Cancer Tumorigenesis by Targeting the miR-135b-5p/CSF1 Axis. Frontiers in Oncology. 2021;11:718532.
33.
SongR, ZhaiY, AoL, FullertonD, MengX. MicroRNA-204 Deficiency in Human Aortic Valves Elevates Valvular Osteogenic Activity. International Journal of Molecular Sciences. 2019;21(1).
34.
QiuM, LuY, LiJ, GuJ, JiY, ShaoY, KongX, SunW. Interaction of SOX5 with SOX9 promotes warfarin-induced aortic valve interstitial cell calcification by repressing transcriptional activation of LRP6. Journal of Molecular and Cellular Cardiology. 2021.
35.
ZhangW, ChenL, WuJ, LiJ, ZhangX, XiangY, LiF, WuC, XiangL, RanQ, et al.Long noncoding RNA TUG1 inhibits osteogenesis of bone marrow mesenchymal stem cells via Smad5 after irradiation. Theranostics. 2019;9(8):2198–2208.
36.
RuJ, GuoL, JiY, NiuY. Hydrostatic pressure induces osteogenic differentiation of adipose-derived mesenchymal stem cells through increasing lncRNA-PAGBC. Aging. 2020;12(13):13477–13487.
37.
FangF, ZhangK, ChenZ, WuB. Noncoding RNAs: new insights into the odontogenic differentiation of dental tissue-derived mesenchymalstem cells. Stem Cell Research & Therapy. 2019;10(1):297.
38.
SchmittA, GarciaJ, HungT, FlynnR, ShenY, QuK, PayumoA, Peres-da-SilvaA, BrozD, BaumR, et al.An inducible long noncoding RNA amplifies DNA damage signaling. Nature Genetics. 2016;48(11):1370–1376.
39.
ZhangG, LanY, XieA, ShiJ, ZhaoH, XuL, ZhuS, LuoT, ZhaoT, XiaoY, et al.Comprehensive analysis of long noncoding RNA (lncRNA)-chromatin interactions reveals lncRNA functions dependent on binding diverse regulatory elements. The Journal of Biological Chemistry. 2019;294(43):15613–15622.
40.
RinnJ, ChangH. Long Noncoding RNAs: Molecular Modalities to Organismal Functions. Annual Review of Biochemistry. 2020;89:283–308.
41.
FanY, LiH, YuZ, DongW, CuiX, MaJ, LiS. Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1. Bioscience Reports. 2020;40(1).
42.
ZhangX, SongL, FengS, DaiX. LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury. Folia Neuropathologica. 2019;57(4):357–365.
43.
GaoS, RenS, LiuY, YanH, ChenX. Targeting EGFR sensitizes 5-Fu-resistant colon cancer cells through modification of the lncRNA-FGD5-AS1-miR-330-3p-Hexokinase 2 axis. Molecular Therapy Oncolytics. 2021;23:14–25.
44.
XiaY, WangW, ShenW, XuK, HuY, HanG, LiuY. Thalidomide suppresses angiogenesis and immune evasion via lncRNA FGD5-AS1/miR-454-3p/ZEB1 axis-mediated VEGFA expression and PD-1/PD-L1 checkpoint in NSCLC. Chemico-Biological Interactions. 2021:109652.
45.
YangY, DongM, HuH, MinQ, XiaoL. LncRNA FGD5-AS1/miR-5590-3p axis facilitates the proliferation and metastasis of renal cell carcinoma through ERK/AKT signalling. European Review for Medical and Pharmacological Sciences. 2020;24(17):8756–8766.
46.
RenJ, ZhangF, WangJ, TangJ. LINC01315 promotes the aggressive phenotypes of papillary thyroid cancer cells by sponging miR-497-5. The Kaohsiung Journal of Medical Sciences2021;37(6):459–467.
47.
ZhuW, ZhangH, GaoJ, XuY. Silencing of miR-497-5p inhibits cell apoptosis and promotes autophagy in Parkinson’s disease by upregulation of FGF2. Environmental Toxicology. 2021.
48.
SongK, YuP, ZhangC, YuanZ, ZhangH. The LncRNA FGD5-AS1/miR-497-5p axis regulates septin 2 (SEPT2) to accelerate cancer progression and increase cisplatin-resistance in laryngeal squamous cell carcinoma. Molecular Carcinogenesis. 2021;60(7):469–480.
49.
LiJ, LeiC, ChenB, ZhuQ. LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p. Frontiers in Oncology. 2021;11:671853.
50.
DaiJ, ZhuB, LinW, GaoH, DaiH, ZhengL, ShiW, ChenW. Identification of prognostic significance of BIRC5 in breast cancer using integrative bioinformatics analysis. Bioscience Reports. 2020;40(2).
51.
MarkovićD, Jevtović-StoimenovT, ĆosićV, StošićB, DinićV, Marković-ŽivkovićB, JankovićR. Clinical Utility of Survivin (BIRC5), Novel Cardiac Biomarker, as a Prognostic Tool Compared to High-sensitivityC-reactive Protein, Heart-type Fatty Acid Binding Protein andRevised Lee Score in Elderly Patients Scheduled for Major Non-cardiac Surgery: A Prospective Pilot Study. Journal of Medical Biochemistry. 2018;37(2):110–120.
52.
ZhaoZ, LiuG, ZhangH, RuanP, GeJ, LiuQ. BIRC5, GAJ5, and lncRNA NPHP3-AS1 Are Correlated with the Development of Atrial Fibrillation-Valvular Heart Disease. International Heart Journal. 2021;62(1):153–161.
53.
GuoZ, ZhaoM, JiaG, MaR, LiM. LncRNA PART1 alleviated myocardial ischemia/reperfusion injury via suppressing miR-503-5p/BIRC5 mediated mitochondrial apoptosis. International Journal of Cardiology. 2021;338:176–184.
54.
ZhangM, YanX, WenP, BaiW, ZhangQ. CircANKRD52 Promotes the Tumorigenesis of Hepatocellular Carcinoma by Sponging miR-497-5p and Upregulating BIRC5 Expression. Cell Transplantation. 2021;30:9636897211008874.
