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Archives of Toxicology

, Volume 93, Issue 11, pp 3261–3276 | Cite as

Upregulation of let-7f-2-3p by long noncoding RNA NEAT1 inhibits XPO1-mediated HAX-1 nuclear export in both in vitro and in vivo rodent models of doxorubicin-induced cardiotoxicity

  • Yanzhuo Liu
  • Chenfan Duan
  • Wen Liu
  • Xuewei Chen
  • Yang Wang
  • Xiaoxiao Liu
  • Jiang Yue
  • Jing Yang
  • Xiaoyang ZhouEmail author
Organ Toxicity and Mechanisms

Abstract

Clinical application of doxorubicin (Dox) is limited due to its undesirable side effects, especially cardiotoxicity. Several microRNAs (miRNAs) such as microRNA-140-5p and miR-23a aggravate Dox-induced cardiotoxicity. Here we demonstrate that upregulation of miRNA let-7f-2-3p by long noncoding RNA (lncRNA) NEAT1 inhibits exportin-1 (XPO1)-mediated nuclear export of hematopoietic-substrate-1 associated protein X-1 (HAX-1) in Dox-induced cardiotoxicity. Treatment of the H9c2 cells with the Dox (1 μM) for 6 h inhibited HAX-1 nuclear export and decreased XPO1 expression. Overexpression of XPO1 significantly attenuated the Dox-induced leakage of myocardial enzymes (creatine phosphokinase, creatine kinase-MB and lactate dehydrogenase) and cardiomyocyte apoptosis with the increased HAX-1 nuclear export. Differentially expressed miRNAs including let-7f-2-3p were selected from the Dox or vehicle-treated cardiomyocytes. TargetScan and luciferase assay showed that let-7f-2-3p targeted XPO1 3′ UTR. Inhibition of let-7f-2-3p reduced Dox-induced cardiotoxicity and apoptosis by inhibiting XPO1-mediated HAX-1 nuclear export, whereas let-7f-2-3p overexpression aggravated these effects. In addition, lncRNA NEAT1 was identified as an endogenous sponge RNA to repress let-7f-2-3p expression. Overexpression of lncRNA NEAT1 abolished the increased let-7f-2-3p expression by Dox, and thereby attenuated cardiotoxicity. The loss function of let-7f-2-3p increased XPO1-mediated HAX-1 nuclear export and reduced myocardial injury in Dox (20 mg/kg)-treated rats. Importantly, let-7f-2-3p inhibition in mice alleviated Dox-induced cardiotoxicity and preserved the antitumor efficacy. Together, let-7f-2-3p regulated by lncRNA NEAT1 aggravates Dox-induced cardiotoxicity through inhibiting XPO1-mediated HAX-1 nuclear export, and may serve as a potential therapeutic target against Dox-induced cardiotoxicity.

Keywords

Doxorubicin Let-7f-2-3p LncRNA NEAT1 XPO1 HAX-1 Cardiotoxicity 

Abbreviations

CK-MB

Creatine kinase-myocardial bound

CPK

Creatine phosphokinase

Dox

Doxorubicin

GEO

Gene Expression Omnibus

HAX-1

Hematopoietic-substrate-1 associated protein X-1

LDH

Lactate dehydrogenase

miRNA

microRNA

XPO1

Exportin 1

Notes

Acknowledgements

This work was partly supported by the National Natural Science Foundation of China [Grant Nos. 81970331 and 81370337 (to Xiaoyang Zhou) and 81872443 (to Jing Yang)], and Medical Science Advancement Program (Basic Medical Science) of Wuhan University, Grant No. TFJC 2018003.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

204_2019_2586_MOESM1_ESM.docx (725 kb)
Supplementary material 1 (DOCX 724 kb)

References

  1. Abdelwahid E, Li H, Wu J, Irioda AC, de Carvalho KA, Luo X (2016) Endoplasmic reticulum (ER) stress triggers Hax1-dependent mitochondrial apoptotic events in cardiac cells. Apoptosis 21:1227–1239.  https://doi.org/10.1007/s10495-016-1286-6 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Archbold HC, Jackson KL, Arora A, Weskamp K, Tank EM, Li X, Miguez R, Dayton RD, Tamir S, Klein RL, Barmada SJ (2018) TDP43 nuclear export and neurodegeneration in models of amyotrophic lateral sclerosis and frontotemporal dementia. Sci Rep 8:4606.  https://doi.org/10.1038/s41598-018-22858-w CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baumann U, Fernández-Sáiz V, Rudelius M, Lemeer S, Rad R, Knorn AM, Slawska J, Engel K, Jeremias I, Li Z, Tomiatti V, Illert AL, Targosz BS, Braun M, Perner S, Leitges M, Klapper W, Dreyling M, Miething C, Lenz G, Rosenwald A, Peschel C, Keller U, Kuster B, Bassermann F (2014) Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis. Nat Med 20:1401–1409.  https://doi.org/10.1038/nm.3740 CrossRefPubMedGoogle Scholar
  4. Bidwell PA, Haghighi K, Kranias EG (2018) The antiapoptotic protein HAX-1 mediates half of phospholamban’s inhibitory activity on calcium cycling and contractility in the heart. J Biol Chem 293:359–367.  https://doi.org/10.1074/jbc.RA117.000128 CrossRefPubMedGoogle Scholar
  5. Camper-Kirby D, Welch S, Walker A, Shiraishi I, Setchell KD, Schaefer E, Kajstura J, Anversa P, Sussman MA (2001) Myocardial Akt activation and gender: increased nuclear activity in females versus males. Circ Res 88:1020–1027CrossRefGoogle Scholar
  6. Camus V, Miloudi H, Taly A, Sola B, Jardin F (2017) XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy. J Hematol Oncol 10:47.  https://doi.org/10.1186/s13045-017-0412-4 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chaudhari U, Nemade H, Gaspar JA, Hescheler J, Hengstler JG, Sachinidis A (2016) MicroRNAs as early toxicity signatures of doxorubicin in human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol 90:3087–3098.  https://doi.org/10.1007/s00204-016-1668-0 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chen G, Li H, Li X, Li B, Zhong L, Huang S, Zheng H, Li M, Jin G, Liao W, Liao Y, Chen Y, Bin J (2018) Loss of long non-coding RNA CRRL promotes cardiomyocyte regeneration and improves cardiac repair by functioning as a competing endogenous RNA. J Mol Cell Cardiol 122:152–164.  https://doi.org/10.1016/j.yjmcc.2018.08.013 CrossRefPubMedGoogle Scholar
  9. Cilenti L, Soundarapandian MM, Kyriazis GA, Stratico V, Singh S, Gupta S, Bonventre JV, Alnemri ES, Zervos AS (2004) Regulation of HAX-1 anti-apoptotic protein by Omi/HtrA2 protease during cell death. J Biol Chem 279:50295–50301.  https://doi.org/10.1074/jbc.M406006200 CrossRefPubMedGoogle Scholar
  10. Conforti F, Zhang X, Rao G, De Pas T, Yonemori Y, Rodriguez JA, McCutcheon JN, Rahhal R, Alberobello AT, Wang Y, Zhang YW, Guha U, Giaccone G (2017) Therapeutic effects of XPO1 inhibition in thymic epithelial tumors. Cancer Res 77:5614–5627.  https://doi.org/10.1158/0008-5472.CAN-17-1323 CrossRefPubMedGoogle Scholar
  11. Deus CM, Zehowski C, Nordgren K, Wallace KB, Skildum A, Oliveira PJ (2015) Stimulating basal mitochondrial respiration decreases doxorubicin apoptotic signaling in H9c2 cardiomyoblasts. Toxicology 334:1–11.  https://doi.org/10.1016/j.tox.2015.05.001 CrossRefPubMedGoogle Scholar
  12. Du J, Hang P, Pan Y, Feng B, Zheng Y, Chen T, Zhao L, Du Z (2019) Inhibition of miR-23a attenuates doxorubicin-induced mitochondria-dependent cardiomyocyte apoptosis by targeting the PGC-1α/Drp1 pathway. Toxicol Appl Pharmacol 369:73–81.  https://doi.org/10.1016/j.taap.2019.02.016 CrossRefPubMedGoogle Scholar
  13. Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N (2017) Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol 35:3942–3948.  https://doi.org/10.1200/JCO.2017.74.1165 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Garg M, Kanojia D, Mayakonda A, Ganesan TS, Sadhanandhan B, Suresh S, Sneha S, Nagare RP, Said JW, Doan NB, Ding LW, Baloglu E, Shacham S, Kauffman M, Koeffler HP (2017) Selinexor (KPT-330) has antitumor activity against anaplastic thyroid carcinoma in vitro and in vivo and enhances sensitivity to doxorubicin. Sci Rep 7:9749.  https://doi.org/10.1038/s41598-017-10325-x CrossRefPubMedPubMedCentralGoogle Scholar
  15. Grzybowska EA, Zayat V, Konopiński R, Trębińska A, Szwarc M, Sarnowska E, Macech E, Korczyński J, Knapp A, Siedlecki JA (2013) HAX-1 is a nucleocytoplasmic shuttling protein with a possible role in mRNA processing. FEBS J 280:256–272.  https://doi.org/10.1111/febs.12066 CrossRefPubMedGoogle Scholar
  16. Gu J, Fan YQ, Zhang HL, Pan JA, Yu JY, Zhang JF, Wang CQ (2018) Resveratrol suppresses doxorubicin-induced cardiotoxicity by disrupting E2F1 mediated autophagy inhibition and apoptosis promotion. Biochem Pharmacol 150:202–213.  https://doi.org/10.1016/j.bcp.2018.02.025 CrossRefPubMedGoogle Scholar
  17. Guo XB, Deng X, Wei Y (2018) Hematopoietic substrate-1-associated protein X-1 regulates the proliferation and apoptosis of endothelial progenitor cells through Akt pathway modulation. Stem Cells 36:406–419.  https://doi.org/10.1002/stem.2741 CrossRefPubMedGoogle Scholar
  18. Han Y, Chen YS, Liu Z, Bodyak N, Rigor D, Bisping E, Pu WT, Kang PM (2006) Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition. Circ Res 99:415–423.  https://doi.org/10.1161/01.RES.0000237387.05259.a5 CrossRefPubMedGoogle Scholar
  19. Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, Fijalkowski M, Nowak R, Fijalkowska M, Volkmann I, Katus HA, Wollert KC, Bauersachs J, Erne P, Lüscher TF, Thum T, Templin C (2014) A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J 35:999–1006.  https://doi.org/10.1093/eurheartj/eht392 CrossRefPubMedGoogle Scholar
  20. Jans DA, Martin AJ, Wagstaff KM (2019) Inhibitors of nuclear transport. Curr Opin Cell Biol 58:50–60.  https://doi.org/10.1016/j.ceb.2019.01.001 CrossRefPubMedGoogle Scholar
  21. Jo A, Choi TG, Jo YH, Jyothi KR, Nguyen MN, Kim JH, Lim S, Shahid M, Akter S, Lee S, Lee KH, Kim W, Cho H, Lee J, Shokat KM, Yoon KS, Kang I, Ha J, Kim SS (2017) Inhibition of carbonyl reductase 1 safely improves the efficacy of doxorubicin in breast cancer treatment. Antioxid Redox Signal 26:70–83.  https://doi.org/10.1089/ars.2015.6457 CrossRefPubMedGoogle Scholar
  22. Lee KH, Cho H, Lee S, Woo JS, Cho BH, Kang JH, Jeong YM, Cheng XW, Kim W (2017) Enhanced-autophagy by exenatide mitigates doxorubicin-induced cardiotoxicity. Int J Cardiol 232:40–47.  https://doi.org/10.1016/j.ijcard.2017.01.123 CrossRefPubMedGoogle Scholar
  23. Levis BE, Binkley PF, Shapiro CL (2017) Cardiotoxic effects of anthracycline-based therapy: what is the evidence and what are the potential harms. Lancet Oncol 18:e445–e456.  https://doi.org/10.1016/S1470-2045(17)30535-1 CrossRefPubMedGoogle Scholar
  24. Li B, Hu Q, Xu R, Ren H, Fei E, Chen D, Wang G (2012) Hax-1 is rapidly degraded by the proteasome dependent on its PEST sequence. BMC Cell Biol 13:20.  https://doi.org/10.1186/1471-2121-13-20 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Luedtke DA, Su Y, Liu S, Edwards H, Wang Y, Lin H, Taub JW, Ge Y (2018) Inhibition of XPO1 enhances cell death induced by ABT-199 in acute myeloid leukaemia via Mcl-1. J Cell Mol Med 22:6099–6111.  https://doi.org/10.1111/jcmm.13886 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Ma M, Hui J, Zhang QY, Zhu Y, He Y, Liu XJ (2018) Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis in streptozotocin-induced diabetic rats. Atherosclerosis 277:113–122.  https://doi.org/10.1016/j.atherosclerosis.2018.08.031 CrossRefPubMedGoogle Scholar
  27. Ming M, Wu W, Xie B, Sukhanova M, Wang W, Kadri S, Sharma S, Lee J, Shacham S, Landesman Y, Maltsev N, Lu P, Wang YL (2018) XPO1 inhibitor selinexor overcomes intrinsic ibrutinib resistance in mantle cell lymphoma via nuclear retention of IκB. Mol Cancer Ther 17:2564–2574.  https://doi.org/10.1158/1535-7163.MCT-17-0789-ATR CrossRefPubMedGoogle Scholar
  28. Molina-Navarro MM, Roselló-Lletí E, Tarazón E, Ortega A, Sánchez-Izquierdo D, Lago F, González-Juanatey JR, García-Pavía P, Salvador A, Montero JA, Portolés M, Rivera M (2013) Heart failure entails significant changes in human nucleocytoplasmic transport gene expression. Int J Cardiol 168:2837–2843.  https://doi.org/10.1016/j.ijcard.2013.03.192 CrossRefPubMedGoogle Scholar
  29. Ozturk M, Ozler M, Kurt YG, Ozturk B, Uysal B, Ersoz N, Yasar M, Demirbas S, Kurt B, Acikel C, Oztas Y, Arpaci F, Topal T, Ozet A, Ataergin S, Kuzhan O, Oter S, Korkmaz A (2011) Efficacy of melatonin, mercaptoethylguanidine and 1400 W in doxorubicin- and trastuzumab-induced cardiotoxicity. J Pineal Res 50:89–96.  https://doi.org/10.1111/j.1600-079X.2010.00818.x CrossRefPubMedGoogle Scholar
  30. Pakravan G, Foroughmand AM, Peymani M, Ghaedi K, Hashemi MS, Hajjari M, Nasr-Esfahani MH (2018) Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells. Cell Death Dis 9:758.  https://doi.org/10.1038/s41419-018-0797-1 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Pereira GC, Pereira SP, Pereira FB, Lourenço N, Lumini JA, Pereira CV, Bjork JA, Magalhães J, Ascensão A, Wieckowski MR, Moreno AJ, Wallace KB, Oliveira PJ (2019) Early cardiac mitochondrial molecular and functional responses to acute anthracycline treatment in wistar rats. Toxicol Sci 169:137–150.  https://doi.org/10.1093/toxsci/kfz026 CrossRefPubMedGoogle Scholar
  32. Prša P, Karademir B, Biçim G, Mahmoud H, Dahan I, Yalçın AS, Mahajna J, Milisav I (2019) The potential use of natural products to negate hepatic, renal and neuronal toxicity induced by cancer therapeutics. Biochem Pharmacol S0006–2952(19):30226–30236.  https://doi.org/10.1016/j.bcp.2019.06.007 (Epub ahead of print) CrossRefGoogle Scholar
  33. Renu K, Abilash VG, Tirupathi Pichiah PB, Arunachalam S (2018) Molecular mechanism of doxorubicin-induced cardiomyopathy-An update. Eur J Pharmacol 818:241–253.  https://doi.org/10.1016/j.ejphar.2017.10.043 CrossRefPubMedGoogle Scholar
  34. Roca-Alonso L, Castellano L, Mills A, Dabrowska AF, Sikkel MB, Pellegrino L, Jacob J, Frampton AE, Krell J, Coombes RC, Harding SE, Lyon AR, Stebbing J (2015) Myocardial miR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis. Cell Death Dis 6:e1754.  https://doi.org/10.1038/cddis.2015.89 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Ruggeri C, Gioffré S, Achilli F, Colombo GI, D’Alessandra Y (2018) Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients. Heart Fail Rev 23:109–122.  https://doi.org/10.1007/s10741-017-9653-0 CrossRefPubMedGoogle Scholar
  36. Sampaio SF, Branco AF, Wojtala A, Vega-Naredo I, Wieckowski MR, Oliveira PJ (2016) p66Shc signaling is involved in stress responses elicited by anthracycline treatment of rat cardiomyoblasts. Arch Toxicol 90:1669–1684.  https://doi.org/10.1007/s00204-015-1583-9 CrossRefPubMedGoogle Scholar
  37. Sheng Z, Xu Y, Wang S, Yuan Y, Huang T, Lu P (2018) XPO1-mediated nuclear export of RNF146 protects from angiotensin II-induced endothelial cellular injury. Biochem Biophys Res Commun 503:1544–1549.  https://doi.org/10.1016/j.bbrc.2018.07.077 CrossRefPubMedGoogle Scholar
  38. Tajiri N, De La Peña I, Acosta SA, Kaneko Y, Tamir S, Landesman Y, Carlson R, Shacham S, Borlongan CV (2016) A nuclear attack on traumatic brain injury: sequestration of cell death in the nucleus. CNS Neurosci Ther 22:306–315.  https://doi.org/10.1111/cns.12501 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Tomita S, Ishida M, Nakatani T, Fukuhara S, Hisashi Y, Ohtsu Y, Suga M, Yutani C, Yagihara T, Yamada K, Kitamura S (2004) Bone marrow is a source of regenerated cardiomyocytes in doxorubicin-induced cardiomyopathy and granulocyte colony-stimulating factor enhances migration of bone marrow cells and attenuates cardiotoxicity of doxorubicin under electron microscopy. J Heart Lung Transplant 23:577–584.  https://doi.org/10.1016/j.healun.2003.06.001 CrossRefPubMedGoogle Scholar
  40. Turner JG, Dawson JL, Grant S, Shain KH, Dalton WS, Dai Y, Meads M, Baz R, Kauffman M, Shacham S, Sullivan DM (2016) Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors. J Hematol Oncol 9:73.  https://doi.org/10.1186/s13045-016-0304-z CrossRefPubMedPubMedCentralGoogle Scholar
  41. Wang JX, Zhang XJ, Feng C, Sun T, Wang K, Wang Y, Zhou LY, Li PF (2015) MicroRNA-532-3p regulates mitochondrial fission through targeting apoptosis repressor with caspase recruitment domain in doxorubicin cardiotoxicity. Cell Death Dis 6:e1677.  https://doi.org/10.1038/cddis.2015.41 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wang K, Liu F, Liu CY, An T, Zhang J, Zhou LY, Wang M, Dong YH, Li N, Gao JN, Zhao YF, Li PF (2016) The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873. Cell Death Differ 23:1394–1405.  https://doi.org/10.1038/cdd.2016.28 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Yan H, Liang H, Liu L, Chen D, Zhang Q (2019) Long noncoding RNA NEAT1 sponges miR-125a-5p to suppress cardiomyocyte apoptosis via BCL2L12. Mol Med Rep 19:4468–4474.  https://doi.org/10.3892/mmr.2019.10095 CrossRefPubMedGoogle Scholar
  44. Yang Y, Zhang H, Li X, Yang T, Jiang Q (2015) Effects of PPARα/PGC-1α on the energy metabolism remodeling and apoptosis in the doxorubicin induced mice cardiomyocytes in vitro. Int J Clin Exp Pathol 8:12216–12224PubMedPubMedCentralGoogle Scholar
  45. Zamorano JL, Lancellotti P, Rodriguez MD, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM, ESC Scientific Document Group (2017) 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur J Heart Fail 19:9–42.  https://doi.org/10.1093/eurheartj/ehw211 CrossRefPubMedGoogle Scholar
  46. Zhang J, Zhao B, Chen X, Wang Z, Xu H, Huang B (2018) Silence of long noncoding RNA NEAT1 inhibits malignant biological behaviors and chemotherapy resistance in gastric cancer. Pathol Oncol Res 24:109–113.  https://doi.org/10.1007/s12253-017-0233-3 CrossRefPubMedGoogle Scholar
  47. Zhao L, Qi Y, Xu L, Tao X, Han X, Yin L, Peng J (2018a) MicroRNA-140-5p aggravates doxorubicin-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2. Redox Biol 15:284–296.  https://doi.org/10.1016/j.redox.2017.12.013 CrossRefPubMedGoogle Scholar
  48. Zhao L, Tao X, Qi Y, Xu L, Yin L, Peng J (2018b) Protective effect of dioscin against doxorubicin-induced cardiotoxicity via adjusting microRNA-140-5p-mediated myocardial oxidative stress. Redox Biol 16:189–198.  https://doi.org/10.1016/j.redox.2018.02.026 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Cardiology, Renmin HospitalWuhan UniversityWuhanChina
  2. 2.Department of Pharmacology and Hubei Province Key Laboratory of Allergy and Immune-related Diseases, School of Basic Medical SciencesWuhan UniversityWuhanChina
  3. 3.Department of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanChina

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