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Circular RNAs: Novel rising stars in cardiovascular disease research
International Journal of Cardiology 202 (2016) 726–727
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Circular RNAs: Novel rising stars in cardiovascular disease research Huibo Wang, Jun Yang ⁎, Jian Yang, Zhixing Fan, Chaojun Yang Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China
a r t i c l e
i n f o
Article history: Received 23 September 2015 Accepted 4 October 2015 Available online 9 October 2015
Dear Editor, Cardiovascular diseases (CVD) still represent the predominant cause of morbidity and mortality worldwide, although the age-standardized mortality from CVD has been halved by better prevention (lifestyle changes and risk factor control) and wider use of appropriate treatments for acute events [1]. A comprehensive review of the literature shows that there are more than 100 cardiovascular disease risk models, such as hypertension, coronary heart disease, heart failure, and so on [2]. Over the past 20 years, there have been dramatic changes in the diagnosis and treatment of CVD, but there is still a clinical need for a novel diagnostic biomarker and new therapeutic interventions to decrease the hospitalization rates and mortality as well as improve the quality of life [3]. Circular RNAs (circRNAs) were recently discovered as a special class of endogenous noncoding RNAs, which have been detected in viruses, plants, archaea, and animals. Unlike linear RNAs, they are covalently closed loop structures without 5′ cap and 3′ polyadenylation tail (poly-(A) tail) and high tissue-specific expression [4]. Several researchers have confirmed that as a kind of competing endogenous RNAs (ceRNAs), circRNAs regulate other RNA transcripts by competing for or sharing the same microRNAs (miRNAs). So they can also be called as miRNA sponge regulators of splicing and transcription and modifiers of parental gene expression [5]. CircRNAs are mainly generated from exonic/intronic sequences and reverse complementary sequences or RNAbinding proteins are necessary for its biogenesis [5]. Emerging evidence indicates that very few circRNAs contain not less than 10 binding sites for a miRNA and many circRNAs only contain smaller numbers of putative miRNA binding sites [6]. miRNAs are small (21–25 nt) single-stranded, evolutionarily conserved non-protein-coding RNAs, which control diverse cellular ⁎ Corresponding author at: Department of Cardiology, The First College of Clinical Medical Sciences, Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, Yiling Road 183, China. E-mail address: [email protected] (J. Yang).
http://dx.doi.org/10.1016/j.ijcard.2015.10.051 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
functions by interacting with the 3′ untranslated region (UTR) of specific target messenger RNAs at the post-transcriptional level [7]. miRNAs play a significant role in regulating fundamental cellular processes (such as cell proliferation, differentiation, apoptosis, migration) and play critical roles in disease initiation and progression [8]. Numerous studies have confirmed that miRNAs are closely related to cardiovascular disease, which are potential emerging biomarkers with extreme sensitivity for early diagnosis and novel treatment for CVD [3]. Therefore, as a kind of miRNA sponge, circRNAs contain complementary binding sites, which can “sponge up” miRNAs of a particular family and serve as competitive inhibitors that suppress the ability of the miRNAs to bind with their mRNA targets [9] (Fig. 1). For example, ciRS-7 (a kind of circRNA) is encoded in the genome antisense to the human CDR1 gene (also termed CDR1as), which contains over 70 conserved seed matches for miRNA-7 and as a miRNA-7 inhibitor. The increase of the expression of ciRS-7 efficiently tethers miRNA-7 and reduces miRNA-7 activity [10]. Ren XP found that miR-7 was up-regulated in murine hearts after myocardial ischemia–reperfusion (I/R) through a microarray assay [11]. Bin L [12] confirmed that miR-7a/b protects myocardial cells against I/R-induced apoptosis by down-regulating PARP expression both in vivo and in vitro. As a result, we can infer that ciRS-7 may aggravate myocardial I/R by tethering miRNA-7. Similar to the former finding, SRY (sex-determining region Y), another circRNA, contains 16 miRNA-138 binding sites. He SY et al. confirmed that miR-138 protects cardiomyocytes from hypoxia-induced apoptosis, which is mediated mainly via MLK3/JNK/c-jun signaling pathway [13]. We can also infer that SRY may aggravate hypoxia-induced cardiomyocytes apoptosis. However, the current studies of circRNAs on CVD are relatively fragmented. ciRS-7 and SRY are a very small part of circRNAs. The relationship between circRNAs and CVD needs further investigation to clarify. But in addition, the study of circRNAs will gradually become one of the most noticeable areas in the field of CVD. I believe that circRNAs will become a novel diagnostic biomarker and new therapeutic interventions for CVD in the soon future. Conflict of interest None. Acknowledgments This work was supported by the National Natural Science Foundation of China (Grant No. 81170133, 81200088 and 81470387), Master's
Correspondence
727
References
Fig. 1. CircRNA functions as a miRNA inhibitor.
Innovation Foundation of China Three Gorges University (2015PY052) and the Natural Science Foundation of Yichang city, China (Grant No. A12301-01) as well as Hubei Province's Outstanding Medical Academic Leader program, China.
[1] S. Yusuf, D. Wood, J. Ralston, et al., The World Heart Federation's vision for worldwide cardiovascular disease prevention, Lancet 386 (9991) (2015) 399–402. [2] K.G.M. Moons, E. Schuit, K.G.M. Moons, et al., Prediction of cardiovascular disease worldwide, Lancet Diabetes Endocrinol. 3 (5) (2015) 309–310. [3] A.S.M. Sayed, K. Xia, U. Salma, et al., Diagnosis, prognosis and therapeutic role of circulating miRNAs in cardiovascular diseases, Heart Lung Circ. 23 (6) (2014) 503–510. [4] L.L. Chen, L. Yang, Regulation of circRNA biogenesis, RNA Biol. 365 (2) (2015) 141–148. [5] S. Qu, X. Yang, X. Li, et al., Circular RNA: a new star of noncoding RNAs, Cancer Lett. 365 (2015) 141–148. [6] W.R. Jeck, N.E. Sharpless, Detecting and characterizing circular RNAs, Nat. Biotechnol. 32 (5) (2014) 453–461. [7] H. Guo, N.T. Ingolia, J.S. Weissman, et al., Mammalian microRNAs predominantly act to decrease target mRNA levels, Nature 466 (7308) (2010) 835–840. [8] D.P. Bartel, MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116 (2) (2004) 281–287. [9] J.Q. Li, J. Yang, P. Zhou, et al., Circular RNAs in cancer: novel insights into origins, properties, functions and implications, Am. J. Cancer Res. 5 (2) (2015) 472–480. [10] Thomas B. Hansen, Jorgen Kjems, K. Christian, et al., Circular RNA and miR-7 in Cancer, Cancer Res. 73 (18) (2013) 5609–5612. [11] X.P. Ren, J.H. Wu, X. Wang, et al., MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20, Circulation 119 (17) (2009) 2357–2366. [12] L. Bin, L. Rui, Z. Chun, et al., MicroRNA-7a/b protects against cardiac myocyte injury in ischemia/reperfusion by targeting poly(ADP-ribose) polymerase, PLoS One 9 (3) (2014), e90096. [13] S.Y. He, P. Liu, Z. Jian, et al., miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway, Biochem. Biophys. Res. Commun. 441 (4) (2013) 763–769.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Circular RNAs: Novel rising stars in cardiovascular disease research Huibo Wang, Jun Yang ⁎, Jian Yang, Zhixing Fan, Chaojun Yang Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China
a r t i c l e
i n f o
Article history: Received 23 September 2015 Accepted 4 October 2015 Available online 9 October 2015
Dear Editor, Cardiovascular diseases (CVD) still represent the predominant cause of morbidity and mortality worldwide, although the age-standardized mortality from CVD has been halved by better prevention (lifestyle changes and risk factor control) and wider use of appropriate treatments for acute events [1]. A comprehensive review of the literature shows that there are more than 100 cardiovascular disease risk models, such as hypertension, coronary heart disease, heart failure, and so on [2]. Over the past 20 years, there have been dramatic changes in the diagnosis and treatment of CVD, but there is still a clinical need for a novel diagnostic biomarker and new therapeutic interventions to decrease the hospitalization rates and mortality as well as improve the quality of life [3]. Circular RNAs (circRNAs) were recently discovered as a special class of endogenous noncoding RNAs, which have been detected in viruses, plants, archaea, and animals. Unlike linear RNAs, they are covalently closed loop structures without 5′ cap and 3′ polyadenylation tail (poly-(A) tail) and high tissue-specific expression [4]. Several researchers have confirmed that as a kind of competing endogenous RNAs (ceRNAs), circRNAs regulate other RNA transcripts by competing for or sharing the same microRNAs (miRNAs). So they can also be called as miRNA sponge regulators of splicing and transcription and modifiers of parental gene expression [5]. CircRNAs are mainly generated from exonic/intronic sequences and reverse complementary sequences or RNAbinding proteins are necessary for its biogenesis [5]. Emerging evidence indicates that very few circRNAs contain not less than 10 binding sites for a miRNA and many circRNAs only contain smaller numbers of putative miRNA binding sites [6]. miRNAs are small (21–25 nt) single-stranded, evolutionarily conserved non-protein-coding RNAs, which control diverse cellular ⁎ Corresponding author at: Department of Cardiology, The First College of Clinical Medical Sciences, Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, Yiling Road 183, China. E-mail address: [email protected] (J. Yang).
http://dx.doi.org/10.1016/j.ijcard.2015.10.051 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
functions by interacting with the 3′ untranslated region (UTR) of specific target messenger RNAs at the post-transcriptional level [7]. miRNAs play a significant role in regulating fundamental cellular processes (such as cell proliferation, differentiation, apoptosis, migration) and play critical roles in disease initiation and progression [8]. Numerous studies have confirmed that miRNAs are closely related to cardiovascular disease, which are potential emerging biomarkers with extreme sensitivity for early diagnosis and novel treatment for CVD [3]. Therefore, as a kind of miRNA sponge, circRNAs contain complementary binding sites, which can “sponge up” miRNAs of a particular family and serve as competitive inhibitors that suppress the ability of the miRNAs to bind with their mRNA targets [9] (Fig. 1). For example, ciRS-7 (a kind of circRNA) is encoded in the genome antisense to the human CDR1 gene (also termed CDR1as), which contains over 70 conserved seed matches for miRNA-7 and as a miRNA-7 inhibitor. The increase of the expression of ciRS-7 efficiently tethers miRNA-7 and reduces miRNA-7 activity [10]. Ren XP found that miR-7 was up-regulated in murine hearts after myocardial ischemia–reperfusion (I/R) through a microarray assay [11]. Bin L [12] confirmed that miR-7a/b protects myocardial cells against I/R-induced apoptosis by down-regulating PARP expression both in vivo and in vitro. As a result, we can infer that ciRS-7 may aggravate myocardial I/R by tethering miRNA-7. Similar to the former finding, SRY (sex-determining region Y), another circRNA, contains 16 miRNA-138 binding sites. He SY et al. confirmed that miR-138 protects cardiomyocytes from hypoxia-induced apoptosis, which is mediated mainly via MLK3/JNK/c-jun signaling pathway [13]. We can also infer that SRY may aggravate hypoxia-induced cardiomyocytes apoptosis. However, the current studies of circRNAs on CVD are relatively fragmented. ciRS-7 and SRY are a very small part of circRNAs. The relationship between circRNAs and CVD needs further investigation to clarify. But in addition, the study of circRNAs will gradually become one of the most noticeable areas in the field of CVD. I believe that circRNAs will become a novel diagnostic biomarker and new therapeutic interventions for CVD in the soon future. Conflict of interest None. Acknowledgments This work was supported by the National Natural Science Foundation of China (Grant No. 81170133, 81200088 and 81470387), Master's
Correspondence
727
References
Fig. 1. CircRNA functions as a miRNA inhibitor.
Innovation Foundation of China Three Gorges University (2015PY052) and the Natural Science Foundation of Yichang city, China (Grant No. A12301-01) as well as Hubei Province's Outstanding Medical Academic Leader program, China.
[1] S. Yusuf, D. Wood, J. Ralston, et al., The World Heart Federation's vision for worldwide cardiovascular disease prevention, Lancet 386 (9991) (2015) 399–402. [2] K.G.M. Moons, E. Schuit, K.G.M. Moons, et al., Prediction of cardiovascular disease worldwide, Lancet Diabetes Endocrinol. 3 (5) (2015) 309–310. [3] A.S.M. Sayed, K. Xia, U. Salma, et al., Diagnosis, prognosis and therapeutic role of circulating miRNAs in cardiovascular diseases, Heart Lung Circ. 23 (6) (2014) 503–510. [4] L.L. Chen, L. Yang, Regulation of circRNA biogenesis, RNA Biol. 365 (2) (2015) 141–148. [5] S. Qu, X. Yang, X. Li, et al., Circular RNA: a new star of noncoding RNAs, Cancer Lett. 365 (2015) 141–148. [6] W.R. Jeck, N.E. Sharpless, Detecting and characterizing circular RNAs, Nat. Biotechnol. 32 (5) (2014) 453–461. [7] H. Guo, N.T. Ingolia, J.S. Weissman, et al., Mammalian microRNAs predominantly act to decrease target mRNA levels, Nature 466 (7308) (2010) 835–840. [8] D.P. Bartel, MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116 (2) (2004) 281–287. [9] J.Q. Li, J. Yang, P. Zhou, et al., Circular RNAs in cancer: novel insights into origins, properties, functions and implications, Am. J. Cancer Res. 5 (2) (2015) 472–480. [10] Thomas B. Hansen, Jorgen Kjems, K. Christian, et al., Circular RNA and miR-7 in Cancer, Cancer Res. 73 (18) (2013) 5609–5612. [11] X.P. Ren, J.H. Wu, X. Wang, et al., MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20, Circulation 119 (17) (2009) 2357–2366. [12] L. Bin, L. Rui, Z. Chun, et al., MicroRNA-7a/b protects against cardiac myocyte injury in ischemia/reperfusion by targeting poly(ADP-ribose) polymerase, PLoS One 9 (3) (2014), e90096. [13] S.Y. He, P. Liu, Z. Jian, et al., miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway, Biochem. Biophys. Res. Commun. 441 (4) (2013) 763–769.