Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

Gan,Jianting; Yuan,Jun; Liu,Yu; Lu,Zhengde; Xue,Yan; Shi,Lei; Zeng,Huayuan

doi:10.3892/ijmm.2019.4441

Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

Authors:
- Jianting Gan
- Jun Yuan
- Yu Liu
- Zhengde Lu
- Yan Xue
- Lei Shi
- Huayuan Zeng
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Affiliations: Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
Published online on: December 23, 2019 https://doi.org/10.3892/ijmm.2019.4441
Pages: 451-460
Copyright: © Gan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Circular RNAs (circRNAs) serve important roles in cardiovascular diseases, including myocardial infarction. However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) are not fully understood. In the present study, the roles of circRNA_101237 and let‑7a‑5p in cardiomyocyte death induced by A/R injury were investigated. It was identified that circRNA_101237 was induced by A/R injury in a time‑dependent manner and that circRNA_101237 knockdown protected cardiomyocytes from A/R‑mediated apoptosis. Additional mechanistic studies revealed that circRNA_101237 served as a sponge for let‑7a‑5p, subsequently regulating insulin‑like growth factor 2 mRNA‑binding protein 3 (IGF2BP3)‑dependent autophagy. IGF2BP3 downregulation decreased the levels of apoptosis and inhibited autophagy induced by A/R challenge in primary cardiomyocytes. These results identified circRNA_101237 as a novel circRNA that regulates cardiomyocyte death and autophagy, and demonstrated that the circRNA‑101237/let‑7a‑5p/IGF2BP3 axis, which serves as a regulator of cardiomyocyte death, may be a potential therapeutic target for the management of cardiovascular diseases.

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1	Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, Zhou LY, Sun T, Wang M, Yu T, et al: A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 37:2602–2611. 2016. View Article : Google Scholar : PubMed/NCBI
2	Jakobi T, Czaja-Hasse LF, Reinhardt R and Dieterich C: Profiling and validation of the circular RNA repertoire in adult murine hearts. Genomics Proteomics Bioinformatics. 14:216–223. 2016. View Article : Google Scholar :
3	Xu S, Zhou L, Ponnusamy M, Zhang L, Dong Y, Zhang Y, Wang Q, Liu J and Wang K: A comprehensive review of circRNA: From purification and identification to disease marker potential. PeerJ. 6:e55032018. View Article : Google Scholar : PubMed/NCBI
4	Li JJ, Wang W, Wang XQ, He Y, Wang SS and Yan YX: A novel strategy of identifying circRNA biomarkers in cardiovascular disease by meta-analysis. J Cell Physiol. 234:21601–21612. 2019. View Article : Google Scholar : PubMed/NCBI
5	Fan X, Weng X, Zhao Y, Chen W, Gan T and Xu D: Circular RNAs in cardiovascular Disease: An overview. Biomed Res Int. 2017:51357812017. View Article : Google Scholar : PubMed/NCBI
6	Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z and Sharpless NE: Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet. 6:e10012332010. View Article : Google Scholar : PubMed/NCBI
7	Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013. View Article : Google Scholar : PubMed/NCBI
8	Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, Li X and Yang BB: Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J. 38:1402–1412. 2017.
9	Zhou Q, Zhang Z, Bei Y, Li G and Wang T: Circular RNAs as novel biomarkers for cardiovascular diseases. Adv Exp Med Biol. 1087:159–170. 2018. View Article : Google Scholar : PubMed/NCBI
10	Wang L, Meng X, Li G, Zhou Q and Xiao J: Circular RNAs in cardiovascular diseases. Adv Exp Med Biol. 1087:191–204. 2018. View Article : Google Scholar : PubMed/NCBI
11	Tan WL, Lim BT, Anene-Nzelu CG, Ackers-Johnson M, Dashi A, See K, Tiang Z, Lee DP, Chua WW, Luu TD, et al: A landscape of circular RNA expression in the human heart. Cardiovasc Res. 113:298–309. 2017.PubMed/NCBI
12	Altesha MA, Ni T, Khan A, Liu K and Zheng X: Circular RNA in cardiovascular disease. J Cell Physiol. 234:5588–5600. 2019. View Article : Google Scholar
13	Kristensen LS, Andersen MS, Stagsted L, Ebbesen KK, Hansen TB and Kjems J: The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 20:675–691. 2019. View Article : Google Scholar : PubMed/NCBI
14	Bayoumi AS, Aonuma T, Teoh JP, Tang YL and Kim IM: Circular noncoding RNAs as potential therapies and circulating biomarkers for cardiovascular diseases. Acta Pharmacol Sin. 39:1100–1109. 2018. View Article : Google Scholar : PubMed/NCBI
15	von Harsdorf R, Li PF and Dietz R: Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation. 99:2934–2941. 1999. View Article : Google Scholar : PubMed/NCBI
16	Fu Y, Liu X, Zhang F, Jiang S, Liu J and Luo Y: Bortezomib-inducible long non-coding RNA myocardial infarction associated transcript is an oncogene in multiple myeloma that suppresses miR-29b. Cell Death Dis. 10:3192019. View Article : Google Scholar : PubMed/NCBI
17	Yang K, Li W, Duan W, Jiang Y, Huang N, Li Y, Ren B and Sun J: Resveratrol attenuates pulmonary embolism associated cardiac injury by suppressing activation of the inflammasome via the MALAT1miR223p signaling pathway. Int J Mol Med. 44:2311–2320. 2019.PubMed/NCBI
18	Kruger J and Rehmsmeier M: RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res. 34(Web Server Issue): W451–W454. 2006. View Article : Google Scholar : PubMed/NCBI
19	Sticht C, De La Torre C, Parveen A and Gretz N: miRWalk: An online resource for prediction of microRNA binding sites. PLoS One. 13:e2062392018. View Article : Google Scholar
20	Wang S, Ye L and Wang L: Protective mechanism of shenmai on myocardial ischemia-reperfusion through the energy metabolism pathway. Am J Transl Res. 11:4046–4062. 2019.PubMed/NCBI
21	Pan JA, Tang Y, Yu JY, Zhang H, Zhang JF, Wang CQ and Gu J: miR-146a attenuates apoptosis and modulates autophagy by targeting TAF9b/P53 pathway in doxorubicin-induced cardio-toxicity. Cell Death Dis. 10:6682019. View Article : Google Scholar
22	Barwari T, Joshi A and Mayr M: MicroRNAs in cardiovascular disease. J Am Coll Cardiol. 68:2577–2584. 2016. View Article : Google Scholar : PubMed/NCBI
23	Romaine SP, Tomaszewski M, Condorelli G and Samani NJ: MicroRNAs in cardiovascular disease: An introduction for clinicians. Heart. 101:921–928. 2015. View Article : Google Scholar : PubMed/NCBI
24	Schulte C, Karakas M and Zeller T: microRNAs in cardiovascular disease-clinical application. Clin Chem Lab Med. 55:687–704. 2017. View Article : Google Scholar
25	Wang K, Gan TY, Li N, Liu CY, Zhou LY, Gao JN, Chen C, Yan KW, Ponnusamy M, Zhang YH and Li PF: Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression. Cell Death Differ. 24:1111–1120. 2017. View Article : Google Scholar : PubMed/NCBI
26	Aufiero S, Reckman YJ, Pinto YM and Creemers EE: Circular RNAs open a new chapter in cardiovascular biology. Nat Rev Cardiol. 16:503–515. 2019. View Article : Google Scholar : PubMed/NCBI
27	E S, Costa MC, Kurc S, Drożdż A, Cortez-Dias N and Enguita FJ: The circulating non-coding RNA landscape for biomarker research: Lessons and prospects from cardiovascular diseases. Acta Pharmacol Sin. 39:1085–1099. 2018. View Article : Google Scholar : PubMed/NCBI
28	Roush S and Slack FJ: The let-7 family of microRNAs. Trends Cell Biol. 18:505–516. 2008. View Article : Google Scholar : PubMed/NCBI
29	Balzeau J, Menezes MR, Cao S and Hagan JP: The LIN28/let-7 pathway in cancer. Front Genet. 8:312017. View Article : Google Scholar : PubMed/NCBI
30	Bao MH, Feng X, Zhang YW, Lou XY, Cheng Y and Zhou HH: Let-7 in cardiovascular diseases, heart development and cardiovascular differentiation from stem cells. Int J Mol Sci. 14:23086–23102. 2013. View Article : Google Scholar : PubMed/NCBI
31	Zhou X, Sun F, Luo S, Zhao W, Yang T, Zhang G, Gao M, Lu R, Shu Y, Mu W, et al: Let-7a is an antihypertrophic regulator in the heart via targeting calmodulin. Int J Biol Sci. 13:22–31. 2017. View Article : Google Scholar : PubMed/NCBI
32	Seeger T, Xu QF, Muhly-Reinholz M, Fischer A, Kremp EM, Zeiher AM and Dimmeler S: Inhibition of let-7 augments the recruitment of epicardial cells and improves cardiac function after myocardial infarction. J Mol Cell Cardiol. 94:145–152. 2016. View Article : Google Scholar : PubMed/NCBI
33	Suarez Y, Fernandez-Hernando C, Pober JS and Sessa WC: Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 100:1164–1173. 2007. View Article : Google Scholar : PubMed/NCBI
34	Cao L, Kong LP, Yu ZB, Han SP, Bai YF, Zhu J, Hu X, Zhu C, Zhu S and Guo XR: microRNA expression profiling of the developing mouse heart. Int J Mol Med. 30:1095–1104. 2012. View Article : Google Scholar : PubMed/NCBI
35	Lederer M, Bley N, Schleifer C and Huttelmaier S: The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer. Semin Cancer Biol. 29:3–12. 2014. View Article : Google Scholar : PubMed/NCBI
36	Bhargava S, Patil V, Shah RA and Somasundaram K: IGF2 mRNA binding protein 3 (IMP3) mediated regulation of transcriptome and translatome in glioma cells. Cancer Biol Ther. 19:42–52. 2018. View Article : Google Scholar :
37	Shimizu T, Sugihara E, Yamaguchi-Iwai S, Tamaki S, Koyama Y, Kamel W, Ueki A, Ishikawa T, Chiyoda T, Osuka S, et al: IGF2 preserves osteosarcoma cell survival by creating an autophagic state of dormancy that protects cells against chemotherapeutic stress. Cancer Res. 74:6531–6541. 2014. View Article : Google Scholar : PubMed/NCBI
38	Nishida K, Yamaguchi O and Otsu K: Crosstalk between autophagy and apoptosis in heart disease. Circ Res. 103:343–351. 2008. View Article : Google Scholar : PubMed/NCBI
39	Takemura G, Kanamori H, Okada H, Miyazaki N, Watanabe T, Tsujimoto A, Goto K, Maruyama R, Fujiwara T and Fujiwara H: Anti-apoptosis in nonmyocytes and pro-autophagy in cardiomyocytes: Two strategies against postinfarction heart failure through regulation of cell death/degeneration. Heart Fail Rev. 23:759–772. 2018. View Article : Google Scholar : PubMed/NCBI