基础研究

LncRNA SENCR靶向miR⁃206调控人主动脉夹层血管平滑肌细胞增殖和凋亡

  • 马润伟 ,
  • 穆纯杰 ,
  • 桂雯婷 ,
  • 邓瑶 ,
  • 赵敏章 ,
  • 柳民 ,
  • 宋怡
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  • 1.云南省阜外心血管病医院,心血管外科,(昆明 650102 )
    2.云南省阜外心血管病医院,体外循环科,(昆明 650102 )

收稿日期: 2023-06-21

  网络出版日期: 2024-02-22

基金资助

云南省“兴滇英才支持计划-名医专项”(YNWR-MY-2020-044);云南省科学技术厅-昆医联合专项课题(202001AY070001-009);心血管疾病国家重点实验室开放课题(2019kfyf-05)

LncRNA SENCR targeted miR⁃206 regulates proliferation and apoptosis of human vascular smooth muscle cells of aortic dissection tissues

  • Runwei MA ,
  • Chunjie MU ,
  • Wenting GUI ,
  • Yao DENG ,
  • Minzhang ZHAO ,
  • Min LIU ,
  • Yi SONG
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  • Department of Cardiothoracic Surgery,Fuwai Yunnan Cardiovascular Hospital,Kunming 650102,China

Received date: 2023-06-21

  Online published: 2024-02-22

摘要

目的 探讨主动脉夹层患者夹层组织中长链非编码RNA SENCR的表达变化及其对人血管平滑肌细胞增殖、凋亡的影响及潜在的分子机制。 方法 HE染色检测夹层组织病理变化,FISH检测夹层组织及人血管平滑肌细胞(HVSMCs)中SENCR的表达,RT-qPCR检测组织中SENCR和miR-206的表达水平。pcDNA3.1-SENCR过表达质粒或空载体pcDNA3.1转染到HVSMCs。CCK-8和Annexin V/PI双染法流式凋亡实验分别检测HVSMCs的增殖和凋亡。双荧光素酶报告验证SENCR和miR?206的靶向关系。 结果 SENCR在HVSMCs中主要定位在胞质和胞核,与正常主动脉组织相比,主动脉夹层组织中SENCR表达下调(P < 0.01),miR?206表达上调(P < 0.01)。过表达SENCR后,HVSMCs细胞增殖能力明显降低(P < 0.01),细胞凋亡水平显著增加(P < 0.01)。SENCR靶向负调控miR-206。 结论 SENCR在主动脉夹层组织中表达下调,过表达SENCR可能通过靶向下调miR?206抑制HVSMCs细胞增殖,促进细胞凋亡。

本文引用格式

马润伟 , 穆纯杰 , 桂雯婷 , 邓瑶 , 赵敏章 , 柳民 , 宋怡 . LncRNA SENCR靶向miR⁃206调控人主动脉夹层血管平滑肌细胞增殖和凋亡[J]. 实用医学杂志, 2024 , 40(3) : 302 -308 . DOI: 10.3969/j.issn.1006-5725.2024.03.004

Abstract

Objective To investigate the expression of lncRNA SENCR in aortic dissection (AD) tissues of AD patients and its effect on and mechanism in the proliferation apoptosis of human vascular smooth muscle cells (HVSMCs). Methods HE staining was done to detect the pathological changes of AD tissues. Fluorescence in situ hybridization (FISH) and RT-qPCR were used to determine the expression of SENCR in the AD tissue and HVSMCs and the expression of SENCR and miR?206 in the tissues, respectively. HVSMCs were cultured and transfected with pcDNA3.1-SENCR overexpression plasmids, or pcDNA3.1 blank plasmid. Then cell proliferation and apoptosis were detected by CCK-8 method and Annexin V/PI double staining flow cytometry assay, respectively. Double luciferase report verified the targeting relationship between SENCR and miR-206. Results SENCR was mainly located in the cytoplasm and nucleus of HVSMCs. Compared with the normal tissue, the expression of SENCR in the AD tissues was down?regulated (P < 0.01), but the expression of miR-206 was up?regulated (P < 0.01). Overexpressed SENCR decreased the cell proliferation of HVSMCs (P < 0.01), but significantly increased the cell apoptosis of HVSMCs (P < 0.01). SENCR could target and negatively regulate miR-206. Conclusion The expression of SENCR is down-regulated in AD tissues, and overexpressed SENCR may inhibit the proliferation and promote the apoptosis of HVSMCs by targeting down?regulated miR?206.

参考文献

1 STOMBAUGH D K, MANGUNTA V R. Aortic Dissection[J]. Anesthesiol Clin, 2022, 40(4):685-703. doi:10.1016/j.anclin.2022.08.012
2 LI Y, REN P, DAWSON A, et al. Single-cell transcriptome analysis reveals dynamic cell populations and differential gene expression patterns in control and aneurysmal human aortic tissue[J]. Circulation, 2020, 142(14):1374-1388. doi:10.1161/circulationaha.120.046528
3 JIANG D, YI X, ZHU X, et al. Experimental in vivo and ex vivo models for the study of human aortic dissection: promises and challenges[J]. Am J Transl Res, 2016, 8(12):5125-5140.
4 WANG Y, ZHAO Z, ZHANG G, et al. Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells[J]. Biochem Biophys Res Commun, 2016, 479(2):358-364. doi:10.1016/j.bbrc.2016.09.080
5 BASATEMUR G L, JORGENSEN H F, CLARKE M C H, et al. Vascular smooth muscle cells in atherosclerosis[J]. Nat Rev Cardiol, 2019, 16(12):727-744. doi:10.1038/s41569-019-0227-9
6 FASOLO F, GREGOLI K D, MAEGDEFESSEL L, et al. Non-coding RNAs in cardiovascular cell biology and atherosclerosis[J]. 2019, 115(12):1732-1756. doi:10.1093/cvr/cvz203
7 FASOLO F, GREGOLI K D, MAEGDEFESSEL L, et al. Non-coding RNAs in cardiovascular cell biology and atherosclerosis[J]. Cardiovasc Res, 2019, 115(12):1732-1756. doi:10.1093/cvr/cvz203
8 SIMION V, ZHOU H, PIERCE J B, et al. LncRNA VINAS regulates atherosclerosis by modulating NF-KB and MAPK signaling[J]. JCI Insight, 2020, 5(21):e140627. doi:10.1172/jci.insight.140627
9 RAPICAVOLI N A, POTH E M, BLACKSHAW S. The long noncoding RNA RNCR2 directs mouse retinal cell specification[J]. BMC Dev Biol, 2010, 10:49. doi:10.1186/1471-213x-10-49
10 KUMARSWAMY R, BAUTERS C, VOLKMANN I, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure[J]. Circ Res, 2014, 114(10):1569-1575. doi:10.1161/circresaha.114.303915
11 YE F, ZHANG J, ZHANG Q, et al. Preliminary study on the mechanism of long noncoding RNA SENCR regulating the proliferation and migration of vascular smooth muscles cells[J]. J Cell Physiol, 2020, 235(12):9635-9643. doi:10.1002/jcp.29775
12 BELL R, LONG X, LIN M, et al. Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA[J]. Arterioscler Thromb Vasc Biol, 2014, 34(6):1249-1259. doi:10.1161/atvbaha.114.303240
13 CAI Z, HUANG J, YANG J, et al. LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation[J]. Boson J Basic Med Sci, 2021, 21(3):323-330.
14 ZOU Z, XU J, LI L, et al. Down-regulation of SENCR promotes smooth muscle cells proliferation and migration in db/db mice through upregulation of FoxO1 and TRPC6[J]. Biomed Pharmacother, 2015, 74:35-41. doi:10.1016/j.biopha.2015.06.009
15 张卓尔,高筱雅,余娟,等. lncRNA KCNQ1OT1靶向miR?129?5p调控帕金森病细胞模型炎症和细胞凋亡的实验研究[J]. 实用医学杂志, 2023, 39(6):672-678.
16 翁旭,武东辉,马文涛,等. lncRNA PCAT19靶向miR?769?5p促进口腔鳞癌HSC3细胞的增殖、迁移和侵袭[J]. 实用医学杂志, 2023, 39(4):417-422.
17 LV Y, FU L, ZHANG Z, et al. Increased Expression of MicroRNA-206 Inhibits Potassium Voltage-Gated Channel Subfamily A Member 5 in Pulmonary Arterial Smooth Muscle Cells and Is Related to Exaggerated Pulmonary Artery Hypertension Following Intrauterine Growth Retardation in Rats[J]. J Am Heart Assoc, 2019, 8(2):e010456. doi:10.1161/jaha.118.010456
18 HE X, WANG S, LI M, et al. Long noncoding RNA GAS5 in duces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis[J]. Theranostics, 2019, 9(19):5558-5576. doi:10.7150/thno.34463
19 WU X, ZHENG X, CHENG J, et al. LncRNA TUG1 regulates proliferation and apoptosis by regulating miR-148b/IGF2 axis in ox LDL-stimulated VSMC and HUVEC[J]. Life Sci, 2020,243:117287. doi:10.1016/j.lfs.2020.117287
20 XU J, ZHANG Y, CHU L, et al. Long non-coding RNA HIF1A AS1 is upregulated in intracranial aneurysms and participates in the regulation of proliferation of vascular smooth muscle cells by upregulating TGF-β1[J]. Exp Ther Med, 2019, 17(3):1797-1801.
21 REN M, TANG T, WEI X, et al. LncRNA H19 regulates smooth muscle cell functions and participates in the development of aortic dissection through sponging miR-193b-3p[J]. Biosci Rep, 2021, 41(1):BSR20202298. doi:10.1042/bsr20202298
22 THUM T, KUMARSWAMY R. The smooth long noncoding RNA SENCR[J]. Arterioscler Thromb Vasc Biol, 2014, 34(6):1124-1125. doi:10.1161/atvbaha.114.303504
23 SONG Y, WANG T, MU C, et al. LncRNA SENCR overexpression attenuated the proliferation, migration and phenotypic switching of vascular smooth muscles cells in aortic dissection via the miR206/myocardin axis[J]. Nutr Metab Cardiovasc Dis, 2022, 32(6):1560-1570. doi:10.1016/j.numecd.2022.03.004
24 TSAI S, HSU L, TSAI H, et al. Aldehyde dehydrogenase 2 protects against abdominal aortic aneurysm formation by reducing reactive oxygen species, vascular inflammation, and apoptosis of vascular smooth muscle cells[J]. FASEB J, 2020, 34(7):9498-9511. doi:10.1096/fj.201902550rrr
25 ZHANG H, BIAN C, TU S, et al. Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in human aortic dissection[J]. BMC Genomic, 2021, 22(1):724. doi:10.1186/s12864-021-08012-3
26 XIA Q, ZHANG L, YAN H, et al. LUCAT1 contributes to MYRF dependent smooth muscle cell apoptosis and may facilitate aneurysm formation via the sequestration of miR-199a-5p[J]. Cell Biol Int, 2020, 44(3):755-763. doi:10.1002/cbin.11270
27 GAO G, ZHANG Y, YU J, et al. Long non-coding RNA MALAT1/microRNA-143/VEGFA signal axis modulates vascular endothelial injury-induced intracranial aneurysm[J]. Nanoscale Res Lett, 2020, 15(1):139. doi:10.1186/s11671-020-03357-2
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