Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation by targeting HAND2

Jing Ma , Shiyu Chen , Lili Hao , Wei Sheng , Weicheng Chen , Xiaojing Ma , Bowen Zhang , Duan Ma , Guoying Huang

Front. Med. ›› 2021, Vol. 15 ›› Issue (1) : 91 -100.

PDF (2545KB)
Front. Med. ›› 2021, Vol. 15 ›› Issue (1) : 91 -100. DOI: 10.1007/s11684-020-0778-5
RESEARCH ARTICLE
RESEARCH ARTICLE

Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation by targeting HAND2

Author information +
History +
PDF (2545KB)

Abstract

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.

Keywords

congenital heart disease / Gene Expression Omnibus / lncRNA SAP30-2:1 / cell proliferation / RNA immunoprecipitation / HAND2

Cite this article

Download citation ▾
Jing Ma, Shiyu Chen, Lili Hao, Wei Sheng, Weicheng Chen, Xiaojing Ma, Bowen Zhang, Duan Ma, Guoying Huang. Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation by targeting HAND2. Front. Med., 2021, 15(1): 91-100 DOI:10.1007/s11684-020-0778-5

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Lara DA, Lopez KN. Public health research in congenital heart disease. Congenit Heart Dis 2014; 9(6): 549–558

[2]

Egbe A, Lee S, Ho D, Uppu S, Srivastava S. Prevalence of congenital anomalies in newborns with congenital heart disease diagnosis. Ann Pediatr Cardiol 2014; 7(2): 86–91

[3]

Andersen TA, Troelsen KdeL, Larsen LA. Of mice and men: molecular genetics of congenital heart disease. Cell Mol Life Sci 2014; 71(8): 1327–1352

[4]

Wang X, Li P, Chen S, Xi L, Guo Y, Guo A, Sun K. Influence of genes and the environment in familial congenital heart defects. Mol Med Rep 2014; 9(2): 695–700

[5]

Zaidi S, Brueckner M. Genetics and genomics of congenital heart disease. Circ Res 2017; 120(6): 923–940

[6]

Scheuermann JC, Boyer LA. Getting to the heart of the matter: long non-coding RNAs in cardiac development and disease. EMBO J 2013; 32(13): 1805–1816

[7]

Cordes KR, Srivastava D. MicroRNA regulation of cardiovascular development. Circ Res 2009; 104(6): 724–732

[8]

Li Y, Huo C, Pan T, Li L, Jin X, Lin X, Chen J, Zhang J, Guo Z, Xu J, Li X. Systematic review regulatory principles of non-coding RNAs in cardiovascular diseases. Brief Bioinform 2019; 20(1): 66–76

[9]

Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell 2009; 136(4): 629–641

[10]

Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription? Sci Adv 2017; 3(9): eaao2110

[11]

Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol 2011; 21(6): 354–361

[12]

Sallam T, Sandhu J, Tontonoz P. Long noncoding RNA discovery in cardiovascular disease: decoding form to function. Circ Res 2018; 122(1): 155–166

[13]

Devaux Y, Zangrando J, Schroen B, Creemers EE, Pedrazzini T, Chang CP, Dorn GW 2nd, Thum T, Heymans S; Cardiolinc Network. Long noncoding RNAs in cardiac development and ageing. Nat Rev Cardiol 2015; 12(7): 415–425

[14]

Jandura A, Krause HM. The new RNA world: growing evidence for long noncoding RNA functionality. Trends Genet 2017; 33(10): 665–676

[15]

Kataoka M, Wang DZ. Noncoding RNAs in cardiovascular disease. In: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Tokyo: Springer, 2016: 313–317

[16]

Zhou Y, He X, Liu R, Qin Y, Wang S, Yao X, Li C, Hu Z. lncRNA CRNDE regulates the proliferation and migration of vascular smooth muscle cells. J Cell Physiol 2019; 234(9): 16205–16214

[17]

Sun R, Zhang L. Long non-coding RNA MALAT1 regulates cardiomyocytes apoptosis after hypoxia/reperfusion injury via modulating miR-200a-3p/PDCD4 axis. Biomed Pharmacother 2019; 111: 1036–1045

[18]

Cheng Z, Zhang Q, Yin A, Feng M, Li H, Liu H, Li Y, Qian L. The long non-coding RNA uc.4 influences cell differentiation through the TGF-β signaling pathway. Exp Mol Med 2018; 50(2): e447

[19]

Hezroni H, Koppstein D, Schwartz MG, Avrutin A, Bartel DP, Ulitsky I. Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Rep 2015; 11(7): 1110–1122

[20]

Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grützner F, Kaessmann H. The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 2014; 505(7485): 635–640

[21]

Song G, Shen Y, Zhu J, Liu H, Liu M, Shen YQ, Zhu S, Kong X, Yu Z, Qian L. Integrated analysis of dysregulated lncRNA expression in fetal cardiac tissues with ventricular septal defect. PLoS One 2013; 8(10): e77492

[22]

Gu M, Zheng A, Tu W, Zhao J, Li L, Li M, Han S, Hu X, Zhu J, Pan Y, Xu J, Yu Z. Circulating lncRNAs as novel, non-invasive biomarkers for prenatal detection of fetal congenital heart defects. Cell Physiol Biochem 2016; 38(4): 1459–1471

[23]

Wang X, Charng WL, Chen CA, Rosenfeld JA, Al Shamsi A, Al-Gazali L, McGuire M, Mew NA, Arnold GL, Qu C, Ding Y, Muzny DM, Gibbs RA, Eng CM, Walkiewicz M, Xia F, Plon SE, Lupski JR, Schaaf CP, Yang Y. Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations. Nat Genet 2017; 49(4): 613–617

[24]

Stallmeyer B, Kuß J, Kotthoff S, Zumhagen S, Vowinkel K, Rinné S, Matschke LA, Friedrich C, Schulze-Bahr E, Rust S, Seebohm G, Decher N, Schulze-Bahr E. A mutation in the G-protein gene GNB2 causes familial sinus node and atrioventricular conduction dysfunction. Circ Res 2017; 120(10): e33–e44

[25]

Wang J, Zhang RR, Cai K, Yang Q, Duan WY, Zhao JY, Gui YH, Wang F. Susceptibility to congenital heart defects associated with a polymorphism in TBX2 3′ untranslated region in the Han Chinese population. Pediatr Res 2019; 85(3): 378–383

[26]

Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell 2018; 172(3): 393–407

[27]

Morikawa Y, Cserjesi P. Cardiac neural crest expression of Hand2 regulates outflow and second heart field development. Circ Res 2008; 103(12): 1422–1429

[28]

Schindler YL, Garske KM, Wang J, Firulli BA, Firulli AB, Poss KD, Yelon D. Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration. Development 2014; 141(16): 3112–3122

[29]

Soemedi R, Wilson IJ, Bentham J, Darlay R, Töpf A, Zelenika D, Cosgrove C, Setchfield K, Thornborough C, Granados-Riveron J, Blue GM, Breckpot J, Hellens S, Zwolinkski S, Glen E, Mamasoula C, Rahman TJ, Hall D, Rauch A, Devriendt K, Gewillig M, O’ Sullivan J, Winlaw DS, Bu’Lock F, Brook JD, Bhattacharya S, Lathrop M, Santibanez-Koref M, Cordell HJ, Goodship JA, Keavney BD. Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease. Am J Hum Genet 2012; 91(3): 489–501

[30]

Vincentz JW, Toolan KP, Zhang W, Firulli AB. Hand factor ablation causes defective left ventricular chamber development and compromised adult cardiac function. PLoS Genet 2017; 13(7): e1006922

[31]

Laurent F, Girdziusaite A, Gamart J, Barozzi I, Osterwalder M, Akiyama JA, Lincoln J, Lopez-Rios J, Visel A, Zuniga A, Zeller R. HAND2 target gene regulatory networks control atrioventricular canal and cardiac valve development. Cell Rep 2017; 19(8): 1602–1613

[32]

Srivastava D. HAND proteins: molecular mediators of cardiac development and congenital heart disease. Trends Cardiovasc Med 1999; 9(1–2): 11–18

[33]

Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 2005; 436(7048): 214–220

[34]

Anderson KM, Anderson DM, McAnally JR, Shelton JM, Bassel-Duby R, Olson EN. Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development. Nature 2016; 539(7629): 433–436

[35]

MacGrogan D, Münch J, de la Pompa JL. Notch and interacting signalling pathways in cardiac development, disease, and regeneration. Nat Rev Cardiol 2018; 15(11): 685–704

[36]

Mollova M, Bersell K, Walsh S, Savla J, Das LT, Park SY, Silberstein LE, Dos Remedios CG, Graham D, Colan S, Kühn B. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U S A 2013; 110(4): 1446–1451

RIGHTS & PERMISSIONS

Higher Education Press

AI Summary AI Mindmap
PDF (2545KB)

Supplementary files

FMD-20029-OF-MD_suppl_1

FMD-20029-OF-MD_suppl_2

5695

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/