Long Noncoding RNA SOX2-OT Aggravates Doxorubicin-Induced Apoptosis of Cardiomyocyte by Targeting MiR-942-5p/DP5

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2021 Feb 19

PMID 33603338

Citations 9

Authors

Haining Wang

Xiule Lin

Jilin Li

Guoning Zeng

Tan Xu

Affiliations

Soon will be listed here.

Abstract

Background: Long non-coding RNAs (LncRNAs) play important roles in doxorubicin (DOX)-induced apoptosis of cardiomyocytes. However, the function of lncRNA SOX2-OT is unclear. This study was carried out to investigate the function of SOX2-OT in doxorubicin-induced cardiomyocyte apoptosis.

Methods: qRT-PCR and immunoblotting were used to detect the expression levels of SOX2-OT, miR-942-5p and death protein-5 (DP5) in DOX-treated primary cardiomyocytes and rat models. The relationship among miR-942-5p, SOX2-OT, and DP5 was explored by luciferase reporter assay. The effects of SOX2-OT, miR-942-5p and DP5 on doxorubicin-induced cardiomyocyte apoptosis were evaluated by Annexin V-FITC/PI method and caspase-3 activity assay. The effect of SOX2-OT on cardiomyocyte apoptosis was analyzed by TUNEL staining and echocardiography.

Results: SOX2-OT and DP5 were highly expressed, while miR-942-5p was down-regulated in DOX-treated primary cardiomyocytes and rat model. SOX2-OT can upregulate DP5 as a sponge of miR-942-5p, which was a direct target of miR-942-5p. In addition, miR-942-5p reversed the protective effect of knockdown of SOX2-OT on cardiomyocytes by inhibiting the expression of DP5 in vitro and in vivo.

Conclusion: Knockdown of SOX2-OT down-regulated DP5 via sponging miR-942-5p and inhibiting DOX-induced apoptosis of primary cardiomyocytes.

Citing Articles

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.

SOX2-OT Binds with ILF3 to Promote Head and Neck Cancer Progression by Modulating Crosstalk between STAT3 and TGF-β Signaling.

Wang R, Yang Y, Wang L, Shi Q, Ma H, He S Cancers (Basel). 2023; 15(24).

PMID: 38136312 PMC: 10742126. DOI: 10.3390/cancers15245766.

DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes.

Distefano R, Ilieva M, Madsen J, Rennie S, Uchida S Noncoding RNA. 2023; 9(4).

PMID: 37489459 PMC: 10366827. DOI: 10.3390/ncrna9040039.

Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.

Nukala S, Jousma J, Yan G, Han Z, Kwon Y, Cho Y Cardiovasc Res. 2023; 119(10):1997-2013.

PMID: 37267414 PMC: 10439712. DOI: 10.1093/cvr/cvad087.

Comparative Analysis of Non-Coding RNA Transcriptomics in Heart Failure.

Garcia-Padilla C, Lozano-Velasco E, Garcia-Lopez V, Aranega A, Franco D, Garcia-Martinez V Biomedicines. 2022; 10(12).

PMID: 36551832 PMC: 9775550. DOI: 10.3390/biomedicines10123076.

References

Han P, Li W, Lin C, Yang J, Shang C, Nuernberg S . A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 2014; 514(7520):102-106. PMC: 4184960. DOI: 10.1038/nature13596. View

Xue Z, Hennelly S, Doyle B, Gulati A, Novikova I, Sanbonmatsu K . A G-Rich Motif in the lncRNA Braveheart Interacts with a Zinc-Finger Transcription Factor to Specify the Cardiovascular Lineage. Mol Cell. 2016; 64(1):37-50. PMC: 6728430. DOI: 10.1016/j.molcel.2016.08.010. View

Farazi T, Spitzer J, Morozov P, Tuschl T . miRNAs in human cancer. J Pathol. 2010; 223(2):102-15. PMC: 3069496. DOI: 10.1002/path.2806. View

Zhang K, Wang Y, Wang Y, Song Y, Zhu J, Si P . Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling. Gene. 2017; 619:10-20. DOI: 10.1016/j.gene.2017.03.038. View

Ultimo S, Zauli G, Martelli A, Vitale M, McCubrey J, Capitani S . Cardiovascular disease-related miRNAs expression: potential role as biomarkers and effects of training exercise. Oncotarget. 2018; 9(24):17238-17254. PMC: 5908320. DOI: 10.18632/oncotarget.24428. View

Ishii M, Mueller I, Nakajima T, Pasquale E, Ogawa K . EphB signaling inhibits gap junctional intercellular communication and synchronized contraction in cultured cardiomyocytes. Basic Res Cardiol. 2011; 106(6):1057-68. DOI: 10.1007/s00395-011-0219-3. View

Akbari-Birgani S, Hosseinkhani S, Mollamohamadi S, Baharvand H . Delay in apoptosome formation attenuates apoptosis in mouse embryonic stem cell differentiation. J Biol Chem. 2014; 289(24):16905-13. PMC: 4059134. DOI: 10.1074/jbc.M113.536730. View

Chen L, Yan K, Liu X, Wang W, Li C, Li M . Valsartan regulates TGF-β/Smads and TGF-β/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure. Arch Pharm Res. 2017; 41(1):101-109. DOI: 10.1007/s12272-017-0980-4. View

Dokanehiifard S, Soltani B, Ghiasi P, Baharvand H, Ganjali M, Hosseinkhani S . hsa-miR-766-5p as a new regulator of mitochondrial apoptosis pathway for discriminating of cell death from cardiac differentiation. Gene. 2020; 736:144448. DOI: 10.1016/j.gene.2020.144448. View

10.

Bartlett J, Trivedi P, Pulinilkunnil T . Autophagic dysregulation in doxorubicin cardiomyopathy. J Mol Cell Cardiol. 2017; 104:1-8. DOI: 10.1016/j.yjmcc.2017.01.007. View

11.

Goretti E, Wagner D, Devaux Y . miRNAs as biomarkers of myocardial infarction: a step forward towards personalized medicine?. Trends Mol Med. 2014; 20(12):716-25. DOI: 10.1016/j.molmed.2014.10.006. View

12.

Wang W, Wang Y, Hu Y, Lin Q, Chen R, Liu H . HDncRNA: a comprehensive database of non-coding RNAs associated with heart diseases. Database (Oxford). 2018; 2018. PMC: 6059085. DOI: 10.1093/database/bay067. View

13.

Kavazis A, Morton A, Hall S, Smuder A . Effects of doxorubicin on cardiac muscle subsarcolemmal and intermyofibrillar mitochondria. Mitochondrion. 2016; 34:9-19. PMC: 5422146. DOI: 10.1016/j.mito.2016.10.008. View

14.

Wang K, Liu F, Liu C, An T, Zhang J, Zhou L . The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873. Cell Death Differ. 2016; 23(8):1394-405. PMC: 4947670. DOI: 10.1038/cdd.2016.28. View

15.

Wei Y, Gao L, Wang L, Shi L, Wei E, Zhou B . Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy. Drug Deliv. 2017; 24(1):681-691. PMC: 8241003. DOI: 10.1080/10717544.2017.1309475. View

16.

Rosenwald S, Gilad S, Benjamin S, Lebanony D, Dromi N, Faerman A . Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin. Mod Pathol. 2010; 23(6):814-23. DOI: 10.1038/modpathol.2010.57. View

17.

Shafiee M, Aleyasin S, Mowla S, Vasei M, Yazdanparast S . The Effect of MicroRNA-375 Overexpression, an Inhibitor of -Induced Carcinogenesis, on lncRNA SOX2OT. Jundishapur J Microbiol. 2016; 9(9):e23464. PMC: 5081003. DOI: 10.5812/jjm.23464. View

18.

Kumral A, Genc S, Ozer E, Yilmaz O, Gokmen N, Koroglu T . Erythropoietin downregulates bax and DP5 proapoptotic gene expression in neonatal hypoxic-ischemic brain injury. Biol Neonate. 2005; 89(3):205-10. DOI: 10.1159/000089951. View

19.

Mitry M, Edwards J . Doxorubicin induced heart failure: Phenotype and molecular mechanisms. Int J Cardiol Heart Vasc. 2016; 10:17-24. PMC: 4871279. DOI: 10.1016/j.ijcha.2015.11.004. View

20.

Jones Buie J, Goodwin A, Cook J, Halushka P, Fan H . The role of miRNAs in cardiovascular disease risk factors. Atherosclerosis. 2016; 254:271-281. PMC: 5125538. DOI: 10.1016/j.atherosclerosis.2016.09.067. View