Long non‑coding RNA XIST promotes the proliferation of cardiac fibroblasts and the accumulation of extracellular matrix by sponging microRNA‑155‑5p

Zhang,Hongbin; Ma,Jianfei; Liu,Fei; Zhang,Jun

doi:10.3892/etm.2021.9908

Long non‑coding RNA XIST promotes the proliferation of cardiac fibroblasts and the accumulation of extracellular matrix by sponging microRNA‑155‑5p

Authors:
- Hongbin Zhang
- Jianfei Ma
- Fei Liu
- Jun Zhang
View Affiliations

Affiliations: Department of Cardiology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
Published online on: March 12, 2021 https://doi.org/10.3892/etm.2021.9908
Article Number: 477
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Acute myocardial infarction (AMI) is characterized by cardiomyocyte death followed by myocardial fibrosis, eventually leading to heart failure. Long non‑coding (lnc)RNA X‑inactive specific transcript (XIST) serves a vital role in the regulation of fibrosis. The aim of the present study was to determine whether myocardial fibrosis may be regulated by XIST and to elucidate the underlying mechanism. The relative mRNA expression levels of the target genes were evaluated using reverse transcription‑quantitative polymerase chain reaction. Cell viability and apoptosis were determined using a Cell Counting Kit‑8 assay and flow cytometry, respectively. The apoptosis and fibrosis‑related protein expression levels were detected using western blot analysis. Finally, the interaction between XIST and microRNA (miR)‑155‑5p was analyzed using a luciferase reporter assay. XIST‑overexpression increased proliferation and the expression level of the fibrosis‑related proteins in the human cardiac fibroblast cells (HCFs). XIST directly targeted miR‑155‑5p and downregulated its expression, while miR‑155‑5p downregulation abolished the effect of XIST‑silencing on cell viability and the expression level of the fibrosis‑related proteins in the HCFs. XIST promoted cell proliferation and the expression level of fibrosis‑related proteins by sponging miR‑155‑5p. Therefore, XIST may represent a novel effective target for AMI treatment.

View Figures

View References

1	Davidson SM, Ferdinandy P, Andreadou I, Bøtker HE, Heusch G, Ibáñez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ, et al: Multitarget strategies to reduce myocardial ischemia/reperfusion injury: JACC review topic of the week. J Am Coll Cardiol. 73:89–99. 2019.PubMed/NCBI View Article : Google Scholar
2	Kurose H and Mangmool S: Myofibroblasts and inflammatory cells as players of cardiac fibrosis. Arch Pharm Res. 39:1100–1113. 2016.PubMed/NCBI View Article : Google Scholar
3	Cho N, Razipour SE and McCain ML: Featured Article: TGF-β1 1 dominates extracellular matrix rigidity for inducing differentiation of human cardiac fibroblasts to myofibroblasts. Exp Biol Med (Maywood). 243:601–612. 2018.PubMed/NCBI View Article : Google Scholar
4	Yuan X, Pan J, Wen L, Gong B, Li J, Gao H, Tan W, Liang S, Zhang H and Wang X: MiR-144-3p enhances cardiac fibrosis after myocardial infarction by targeting PTEN. Front Cell Dev Biol. 7(249)2019.PubMed/NCBI View Article : Google Scholar
5	Puvvula PK: LncRNAs regulatory networks in cellular senescence. Int J Mol Sci. 20(2615)2019.PubMed/NCBI View Article : Google Scholar
6	Yarani R, Mirza AH, Kaur S and Pociot F: The emerging role of lncRNAs in inflammatory bowel disease. Exp Mol Med. 50:1–14. 2018.PubMed/NCBI View Article : Google Scholar
7	Xiao L, Gu Y, Sun Y, Chen J, Wang X, Zhang Y, Gao L and Li L: The long noncoding RNA XIST regulates cardiac hypertrophy by targeting miR-101. J Cell Physiol. 234:13680–13692. 2019.PubMed/NCBI View Article : Google Scholar
8	McKiernan PJ, Molloy K, Cryan SA, McElvaney NG and Greene CM: Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium. Int J Biochem Cell Biol. 52:184–191. 2014.PubMed/NCBI View Article : Google Scholar
9	Wang Y, Liang Y, Luo J, Nie J, Yin H, Chen Q, Dong J, Zhu J, Xia J and Shuai W: XIST/miR-139 axis regulates bleomycin (BLM)-induced extracellular matrix (ECM) and pulmonary fibrosis through β-catenin. Oncotarget. 8:65359–65369. 2017.PubMed/NCBI View Article : Google Scholar
10	Yang J, Shen Y, Yang X, Long Y, Chen S, Lin X, Dong R and Yuan J: Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A. Am J Physiol Renal Physiol. 317:F1350–F1358. 2019.PubMed/NCBI View Article : Google Scholar
11	Liu Y, Gao L, Guo S, Zhao X, Li R, Yan X, Li Y, Wang S, Niu X, Yao L, et al: Kaempferol alleviates angiotensin II-induced cardiac dysfunction and interstitial fibrosis in mice. Cell Physiol Biochem. 43:2253–2263. 2017.PubMed/NCBI View Article : Google Scholar
12	Wang ZF, Wang NP, Harmouche S, Philip T, Pang XF, Bai F and Zhao ZQ: Postconditioning attenuates coronary perivascular and interstitial fibrosis through modulating angiotensin II receptors and Angiotensin-converting enzyme 2 after myocardial infarction. J Surg Res. 211:178–190. 2017.PubMed/NCBI View Article : Google Scholar
13	Lin C, Wei D, Xin D, Pan J and Huang M: Ellagic acid inhibits proliferation and migration of cardiac fibroblasts by Down-regulating expression of HDAC1. J Toxicol Sci. 44:425–433. 2019.PubMed/NCBI View Article : Google Scholar
14	Tang CM, Zhang M, Huang L, Hu ZQ, Zhu JN, Xiao Z, Zhang Z, Lin QX, Zheng XL, Yang M, et al: CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts. Sci Rep. 7(40342)2017.PubMed/NCBI View Article : Google Scholar
15	Zhao N, Yu H, Sun M, Zhang Y, Xu M and Gao W: MiRNA-711-SP1-collagen-I pathway is involved in the anti-fibrotic effect of pioglitazone in myocardial infarction. Sci China Life Sci. 56:431–439. 2013.PubMed/NCBI View Article : Google Scholar
16	Maruyama T, Nishihara K, Umikawa M, Arasaki A, Nakasone T, Nimura F, Matayoshi A, Takei K, Nakachi S, Kariya KI, et al: MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma. Oncol Lett. 15:2349–2363. 2018.PubMed/NCBI View Article : Google Scholar
17	Castro-Dominguez Y, Dharmarajan K and McNamara RL: Predicting death after acute myocardial infarction. Trends Cardiovasc Med. 28:102–109. 2018.PubMed/NCBI View Article : Google Scholar
18	Yin Y, Zhang Q, Zhao Q, Ding G, Wei C, Chang L, Li H, Bei H, Wang H, Liang J, et al: Tongxinluo attenuates myocardiac fibrosis after acute myocardial infarction in rats via inhibition of endothelial-to-mesenchymal transition. Biomed Res Int. 2019(6595437)2019.PubMed/NCBI View Article : Google Scholar
19	van Putten S, Shafieyan Y and Hinz B: Mechanical control of cardiac myofibroblasts. J Mol Cell Cardiol. 93:133–142. 2016.PubMed/NCBI View Article : Google Scholar
20	Xie ZY, Wang FF, Xiao ZH, Liu SF, Lai YL and Tang SL: Long noncoding RNA XIST enhances ethanol-induced hepatic stellate cells autophagy and activation via miR-29b/HMGB1 axis. IUBMB Life. 71:1962–1972. 2019.PubMed/NCBI View Article : Google Scholar
21	Chen L, Zheng SY, Yang CQ, Ma BM and Jiang D: MiR-155-5p inhibits the proliferation and migration of VSMCs and HUVECs in atherosclerosis by targeting AKT1. Eur Rev Med Pharmacol Sci. 23:2223–2233. 2019.PubMed/NCBI View Article : Google Scholar
22	Zhang Z, Liang K, Zou G, Chen X, Shi S, Wang G, Zhang K, Li K and Zhai S: Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating macrophage-mediated inflammation. Biosci Rep. 38(BSR20171432)2018.PubMed/NCBI View Article : Google Scholar
23	Chen NX, Kiattisunthorn K, O'Neill KD, Chen X, Moorthi RN, Gattone VH II, Allen MR and Moe SM: Decreased microRNA is involved in the vascular remodeling abnormalities in chronic kidney disease (CKD). PLoS One. 8(e64558)2013.PubMed/NCBI View Article : Google Scholar
24	Zhang G, Shi H, Wang L, Zhou M, Wang Z, Liu X, Cheng L, Li W and Li X: MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction. PLoS One. 10(e0135339)2015.PubMed/NCBI View Article : Google Scholar
25	Zhao F, Wu Y, Yang W, Wu D, Wang C and Zhang F: Inhibition of vascular calcification by microRNA-155-5p is accompanied by the inactivation of TGF-β1/Smad2/3 signaling pathway. Acta Histochem. 122(151551)2020.PubMed/NCBI View Article : Google Scholar
26	Halper J and Kjaer M: Basic components of connective tissues and extracellular matrix: Elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins. Adv Exp Med Biol. 802:31–47. 2014.PubMed/NCBI View Article : Google Scholar
27	Jabłońska-Trypuć A, Matejczyk M and Rosochacki S: Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 31 (Suppl 1):S177–S183. 2016.PubMed/NCBI View Article : Google Scholar