Long Non-coding RNA Sox2OT Promotes Coronary Microembolization-induced Myocardial Injury by Mediating Pyroptosis

Overview

Journal ESC Heart Fail

Date 2022 Mar 19

PMID 35304834

Authors

Liying Xuan

Danni Fu

Dong Zhen

Dongsong Bai

Lijun Yu

Guohua Gong

Affiliations

Soon will be listed here.

Abstract

Objective: As a common complication of coronary microembolization (CME), myocardial injury (MI) implies high mortality. Long non-coding RNAs (lncRNAs) are rarely studied in CME-induced MI. Herein, this study intended to evaluate the role of lncRNA Sox2 overlapping transcript (Sox2OT) in CME-induced MI.

Methods: The CME rat models were successfully established by injection of microemboli. Rat cardiac functions and MI were observed by ultrasonic electrocardiogram, HE staining, and HBFP staining. Functional assays were utilized to test the inflammatory responses, oxidative stress, and pyroptosis using reverse transcription quantitative polymerase chain reaction, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. Dual-luciferase reporter gene assay and RNA immunoprecipitation were conducted to clarify the targeting relations between Sox2OT and microRNA (miRNA)-23b and between miR-23b and toll-like receptor 4 (TLR4).

Results: Rat CME disrupted the cardiac functions and induced inflammatory responses and oxidative stress, and activated the nuclear factor-kappa B (NF-κB) pathway and pyroptosis (all P < 0.05). An NF-κB inhibitor downregulated the NF-κB pathway, reduced pyroptosis, and relieved cardiomyocyte injury and pyroptosis. Compared with the sham group (1.05 ± 0.32), lncRNA Sox2OT level (4.41 ± 0.67) in the CME group was elevated (P < 0.05). Sox2OT acted as a competitive endogenous RNA (ceRNA) of miR-23b to regulate TLR4. Silencing of Sox2OT favoured miR-23b binding to 3'UTR of TLR4 mRNA leading to suppressed TLR4-mediated NFKB signalling and pyroptosis in myocardial tissues harvested from CME rat models. In addition, miR-23b overexpression could supplement the cytosolic miR-23b reserves to target TLR-4 and partially reverse Sox2OT-mediated pyroptosis in LPS-treated H9C2 cells.

Conclusions: This study supported that silencing Sox2OT inhibited CME-induced MI by eliminating Sox2OT/miR-23b binding and down-regulating the TLR4/NF-κB pathway. This investigation may provide novel insights for the treatment of CME-induced MI.

Citing Articles

Research Progress of Regulatory Cell Death in Coronary Microembolization.

Chang C, Huang W, Cai R, Mo L, Wu Q, Su Q Int J Med Sci. 2025; 22(1):132-139.

PMID: 39744170 PMC: 11659838. DOI: 10.7150/ijms.105295.

The emerging role of long non-coding RNA SOX2-OT in cancers and non-malignant diseases.

Yang J, Tan F, Chen Y, Li X, Yuan C J Physiol Biochem. 2024; .

PMID: 39702742 DOI: 10.1007/s13105-024-01059-2.

Importance of long non-coding RNAs in the pathogenesis, diagnosis, and treatment of myocardial infarction.

Zolfaghari Dehkharghani M, Mousavi S, Kianifard N, Fazlzadeh A, Parsa H, Tavakoli Pirzaman A Int J Cardiol Heart Vasc. 2024; 55:101529.

PMID: 39498345 PMC: 11532444. DOI: 10.1016/j.ijcha.2024.101529.

Long Noncoding RNA SOX2OT Ameliorates Sepsis-Induced Myocardial Injury by Inhibiting Cellular Pyroptosis Through Mediating the EZH2/Nrf-2/NLRP3 Signaling Pathway.

Bai X, Yang L, Liu R, Tang Y, Yang L, Ma L J Inflamm Res. 2024; 17:3115-3127.

PMID: 38774445 PMC: 11107952. DOI: 10.2147/JIR.S451643.

Propofol synergizes with circAPBB2 to protect against hypoxia/reoxygenation-induced oxidative stress, inflammation, and apoptosis of human cardiomyocytes.

Jin C, Yuan S, Piao L, Ren M, Liu Q Immun Inflamm Dis. 2023; 11(8):e952.

PMID: 37647434 PMC: 10408373. DOI: 10.1002/iid3.952.

References

Lei Q, Yi T, Chen C . NF-κB-Gasdermin D (GSDMD) Axis Couples Oxidative Stress and NACHT, LRR and PYD Domains-Containing Protein 3 (NLRP3) Inflammasome-Mediated Cardiomyocyte Pyroptosis Following Myocardial Infarction. Med Sci Monit. 2018; 24:6044-6052. PMC: 6128186. DOI: 10.12659/MSM.908529. View

Li H, Han X, Zuo K, Li L, Liu J, Yuan X . miR-23b promotes cutaneous wound healing through inhibition of the inflammatory responses by targeting ASK1. Acta Biochim Biophys Sin (Shanghai). 2018; 50(11):1104-1113. DOI: 10.1093/abbs/gmy109. View

Pant T, Dhanasekaran A, Fang J, Bai X, Bosnjak Z, Liang M . Current status and strategies of long noncoding RNA research for diabetic cardiomyopathy. BMC Cardiovasc Disord. 2018; 18(1):197. PMC: 6196023. DOI: 10.1186/s12872-018-0939-5. View

Chen M, Guan Y, Li A, Zhao Y, Zhang L, Zhang L . Mediates Mitochondrial Dysfunction in Septic Cardiomyopathy. DNA Cell Biol. 2019; 38(11):1197-1206. DOI: 10.1089/dna.2019.4839. View

Du Y, Gu X, Meng H, Aa N, Liu S, Peng C . Muscone improves cardiac function in mice after myocardial infarction by alleviating cardiac macrophage-mediated chronic inflammation through inhibition of NF-κB and NLRP3 inflammasome. Am J Transl Res. 2019; 10(12):4235-4246. PMC: 6325512. View

Cao C, Zhang Y, Chai Y, Wang L, Yin C, Shou S . Attenuation of Sepsis-Induced Cardiomyopathy by Regulation of MicroRNA-23b Is Mediated Through Targeting of MyD88-Mediated NF-κB Activation. Inflammation. 2019; 42(3):973-986. DOI: 10.1007/s10753-019-00958-7. View

Wu H, Liu J, Li W, Liu G, Li Z . LncRNA-HOTAIR promotes TNF-α production in cardiomyocytes of LPS-induced sepsis mice by activating NF-κB pathway. Biochem Biophys Res Commun. 2016; 471(1):240-6. DOI: 10.1016/j.bbrc.2016.01.117. View

Jia C, Chen H, Zhang J, Zhou K, Zhuge Y, Niu C . Role of pyroptosis in cardiovascular diseases. Int Immunopharmacol. 2018; 67:311-318. DOI: 10.1016/j.intimp.2018.12.028. View

Li S, Fang J, Chen L . Pyrrolidine Dithiocarbamate Attenuates Cardiocyte Apoptosis and Ameliorates Heart Failure Following Coronary Microembolization in Rats. Balkan Med J. 2019; 36(4):245-250. PMC: 6636647. DOI: 10.4274/balkanmedj.galenos.2019.2019.3.8. View

10.

Li L, Li D, Qu N, Wen W, Huang W . The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury. Cardiology. 2010; 117(3):207-15. DOI: 10.1159/000321713. View

11.

Toldo S, Mauro A, Cutter Z, Abbate A . Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2018; 315(6):H1553-H1568. PMC: 6336966. DOI: 10.1152/ajpheart.00158.2018. View

12.

Li Z, Jiang P, Li J, Peng M, Zhao X, Zhang X . Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in pancreatic ductal adenocarcinoma. Oncogene. 2018; 37(28):3822-3838. DOI: 10.1038/s41388-018-0237-9. View

13.

Heusch G, Skyschally A, Kleinbongard P . Coronary microembolization and microvascular dysfunction. Int J Cardiol. 2018; 258:17-23. DOI: 10.1016/j.ijcard.2018.02.010. View

14.

Shen S, Jiang H, Bei Y, Xiao J, Li X . Long Non-Coding RNAs in Cardiac Remodeling. Cell Physiol Biochem. 2017; 41(5):1830-1837. DOI: 10.1159/000471913. View

15.

Su Q, Li L, Sun Y, Yang H, Ye Z, Zhao J . Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury. Cell Physiol Biochem. 2018; 47(4):1497-1508. DOI: 10.1159/000490866. View

16.

Sucharov C, Kao D, Port J, Karimpour-Fard A, Quaife R, Minobe W . Myocardial microRNAs associated with reverse remodeling in human heart failure. JCI Insight. 2017; 2(2):e89169. PMC: 5256135. DOI: 10.1172/jci.insight.89169. View

17.

Shahryari A, Jazi M, Samaei N, Mowla S . Long non-coding RNA SOX2OT: expression signature, splicing patterns, and emerging roles in pluripotency and tumorigenesis. Front Genet. 2015; 6:196. PMC: 4469893. DOI: 10.3389/fgene.2015.00196. View

18.

Boyer L, Lee T, Cole M, Johnstone S, Levine S, Zucker J . Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122(6):947-56. PMC: 3006442. DOI: 10.1016/j.cell.2005.08.020. View

19.

Boon R, Jae N, Holdt L, Dimmeler S . Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets?. J Am Coll Cardiol. 2016; 67(10):1214-1226. DOI: 10.1016/j.jacc.2015.12.051. View

20.

Li C, Wang S, Wang W, Song S, Liu X . Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury. Cell Mol Neurobiol. 2016; 37(2):361-369. PMC: 11482052. DOI: 10.1007/s10571-016-0380-1. View