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MicroRNA-34a targets sirtuin 1 and leads to diabetes-induced testicular apoptotic cell death

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Abstract

Testicular apoptotic cell death (TACD) contributes to diabetes mellitus (DM)-induced male infertility. MicroRNA-34a (miR-34a) is a pro-apoptotic RNA that targets sirtuin 1 (SIRT1) which provides protection against complications of (DM). However, the specific role of miR-34a in (DM)-induced TACD is unknown. MiR-34a targets Sirt1 mRNA, resulting in apoptosis. However, whether or not SIRT1 is a major target of miR-34a in (DM)-induced TACD is unclear. The present study aimed to define the role of miR-34a/SIRT1 in (DM)-induced TACD. C57BL/6 male mice were induced to (DM) by streptozotocin, for a period of 24 weeks. The expression of miR-34a and Sirt1 as well as apoptotic cell death was determined in the testes of the non-diabetic, diabetic, and the miR-34a-specific inhibitor (miR-34a-I)-treated diabetic mice. In addition, the novel SIRT1 activator SRT2104 was delivered to the mice to determine the role of SIRT1 in DM-induced TACD. The diabetic mice developed remarkable testicular oxidative stress, endoplasmic reticulum stress, and apoptotic cell death, the effects of which were significantly and similarly attenuated by both miR-34a-I and SRT2104. Mechanistically, the DM-induced testicular elevation of miR-34a and the decrease in SIRT1 protein were markedly prevented by both miR-34a-I and SRT2104, to a similar extent. The present study demonstrates a critical role of miR-34a/SIRT1 in DM-induced TACD, providing miR-34a inhibition and SIRT1 activation as novel strategies in clinical management of DM-induced male infertility.

Key messages

  • MiR-34a mediates diabetes-induced TACD via inhibition of SIRT1.

  • The novel SIRT1 activator SRT2104 attenuates diabetes-induced TACD.

  • MiR-34a inhibition activates SIRT1 and prevents diabetes-induced TACD.

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References

  1. Alves MG, Martins AD, Rato L, Moreira PI, Socorro S, Oliveira PF (2013) Molecular mechanisms beyond glucose transport in diabetes-related male infertility. Biochim Biophys Acta 1832(5):626–635

    Article  PubMed  CAS  Google Scholar 

  2. Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo A, Solmi M, Stubbs B, Veronese N (2017) High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabet Med 34(9):1185–1192

    Article  PubMed  CAS  Google Scholar 

  3. Malavige LS, Levy JC (2009) Erectile dysfunction in diabetes mellitus. J Sex Med 6(5):1232–1247

    Article  PubMed  Google Scholar 

  4. Ranganathan P, Mahran AM, Hallak J, Agarwal A (2002) Sperm cryopreservation for men with nonmalignant, systemic diseases: a descriptive study. J Androl 23(1):71–75

    Article  PubMed  Google Scholar 

  5. Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, Lewis SEM (2007) Insulin dependant diabetes mellitus: implications for male reproductive function. Hum Reprod 22(7):1871–1877

  6. Mallidis C, Agbaje I, Rogers D, Glenn J, McCullough S, Atkinson AB, Steger K, Stitt A, McClure N (2007) Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus. Hum Reprod 22(8):2169–2177

    Article  PubMed  CAS  Google Scholar 

  7. Jiang X, Bai Y, Zhang Z, Xin Y, Cai L (2014) Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function. Toxicol Appl Pharmacol 279(2):198–210

    Article  PubMed  CAS  Google Scholar 

  8. Wang Y, Zhang Z, Guo W, Sun W, Miao X, Wu H, Cong X, Wintergerst KA, Kong X, Cai L (2014) Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function. Am J Physiol Endocrinol Metab 307(1):E14–E23

    Article  PubMed  CAS  Google Scholar 

  9. Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W, Cai L (2011) Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett 200(1–2):100–106

    Article  PubMed  CAS  Google Scholar 

  10. Zhao Y, Kong C, Chen X, Wang Z, Wan Z, Jia L, Liu Q, Wang Y, Li W, Cui J, Han F, Cai L (2016) Repetitive exposure to low-dose X-irradiation attenuates testicular apoptosis in type 2 diabetic rats, likely via Akt-mediated Nrf2 activation. Mol Cell Endocrinol 422:203–210

    Article  PubMed  CAS  Google Scholar 

  11. Bhatt K, Mi QS, Dong Z (2011) microRNAs in kidneys: biogenesis, regulation, and pathophysiological roles. Am J Physiol Renal Physiol 300(3):F602–F610

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Fernandez-Valverde SL, Taft RJ, Mattick JS (2011) MicroRNAs in beta-cell biology, insulin resistance, diabetes and its complications. Diabetes 60(7):1825–1831

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Wu, H., Kong L., Zhou S., Cui W., Xu F., Luo M., Li X., Tan Y., Miao L., The role of MicroRNAs in diabetic nephropathy. J Diabetes Res, 2014. 2014: p. 920134, 1, 12

  14. Lee YS, Nakahara K, Pham JW, Kim K, He Z, Sontheimer EJ, Carthew RW (2004) Distinct roles for drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117(1):69–81

    Article  PubMed  CAS  Google Scholar 

  15. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107(7):823–826

    Article  PubMed  CAS  Google Scholar 

  16. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  PubMed  CAS  Google Scholar 

  17. Fatemi N, Sanati MH, Shamsara M, Moayer F, Zavarehei MJ, Pouya A, Sayyahpour FA, Ayat H, Gourabi H (2014) TBHP-induced oxidative stress alters microRNAs expression in mouse testis. J Assist Reprod Genet 31(10):1287–1293

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yamakuchi M, Ferlito M, Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A 105(36):13421–13426

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lize M, Pilarski S, Dobbelstein M (2010) E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis. Cell Death Differ 17(3):452–458

    Article  PubMed  CAS  Google Scholar 

  20. Lin Y, Shen J, Li D, Ming J, Liu X, Zhang N, Lai J, Shi M, Ji Q, Xing Y (2017) MiR-34a contributes to diabetes-related cochlear hair cell apoptosis via SIRT1/HIF-1alpha signaling. Gen Comp Endocrinol 246:63–70

    Article  PubMed  CAS  Google Scholar 

  21. Zhang QJ, Li J, Zhang SY (2017) Effects of TRPM7/miR-34a gene silencing on spatial cognitive function and hippocampal neurogenesis in mice with type 1 diabetes mellitus. Mol Neurobiol

  22. Backe, M.B., Novotny G.W., Christensen D.P., Grunnet L.G., Mandrup-Poulsen T., Altering beta-cell number through stable alteration of miR-21 and miR-34a expression. Islets, 2014. 6(1): p. e27754

  23. Guarente L, Picard F (2005) Calorie restriction—the SIR2 connection. Cell 120(4):473–482

    Article  PubMed  CAS  Google Scholar 

  24. Karbasforooshan H, Karimi G (2017) The role of SIRT1 in diabetic cardiomyopathy. Biomed Pharmacother 90:386–392

    Article  PubMed  CAS  Google Scholar 

  25. Wakino S, Hasegawa K, Itoh H (2015) Sirtuin and metabolic kidney disease. Kidney Int 88(4):691–698

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Karbasforooshan H, Karimi G (2017) The role of SIRT1 in diabetic retinopathy. Biomed Pharmacother 97:190–194

    Article  PubMed  CAS  Google Scholar 

  27. Hoffmann E, Wald J, Lavu S, Roberts J, Beaumont C, Haddad J, Elliott P, Westphal C, Jacobson E (2013) Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man. Br J Clin Pharmacol 75(1):186–196

    Article  PubMed  CAS  Google Scholar 

  28. Baksi A, Kraydashenko O, Zalevkaya A, Stets R, Elliott P, Haddad J, Hoffmann E, Vlasuk GP, Jacobson EW (2014) A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes. Br J Clin Pharmacol 78(1):69–77

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Libri V, Brown AP, Gambarota G, Haddad J, Shields GS, Dawes H, Pinato DJ, Hoffman E, Elliot PJ, Vlasuk GP, Jacobson E, Wilkins MR, Matthews PM (2012) A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers. PLoS One 7(12):e51395

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. van der Meer AJ, Scicluna BP, Moerland PD, Lin J, Jacobson EW, Vlasuk GP, van der Poll T (2015) The selective sirtuin 1 activator SRT2104 reduces endotoxin-induced cytokine release and coagulation activation in humans. Crit Care Med 43(6):e199–e202

    Article  PubMed  CAS  Google Scholar 

  31. Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Joshi NV, Mills NL, Hoffmann E, Jacobson EW, Vlasuk GP, Waterhouse BR, Lang NN, Newby DE (2013) Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc 2(3):e000042

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Mills NL, Waterhouse BR, Hoffmann E, Jacobson EW, Lang NN, Frier BM, Newby DE (2016) Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus. Open Heart 3(1):e000402

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sun W, Liu X, Zhang H, Song Y, Li T, Liu X, Liu Y, Guo L, Wang F, Yang T, Guo W, Wu J, Jin H, Wu H (2017) Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1. Free Radic Biol Med 108:840–857

    Article  PubMed  CAS  Google Scholar 

  34. Wu H, Kong L, Cheng Y, Zhang Z, Wang Y, Luo M, Tan Y, Chen X, Miao L, Cai L (2015) Metallothionein plays a prominent role in the prevention of diabetic nephropathy by sulforaphane via up-regulation of Nrf2. Free Radic Biol Med 89:431–442

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Wu H, Kong L, Tan Y, Epstein PN, Zeng J, Gu J, Liang G, Kong M, Chen X, Miao L, Cai L (2016) C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21. Diabetologia 59(7):1558–1568

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Wu H, Wu J, Zhou S, Huang W, Li Y, Zhang H, Wang J, Jia Y (2018) SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition of P53. J Endocrinol 237(1):1–14

    Article  PubMed  Google Scholar 

  37. Pan, C., Zhou S., Wu J., Liu L., Song Y., Li T., Ha L., Liu X., Wang F., Tian J., Wu H., NRF2 plays a critical role in both self and EGCG protection against diabetic testicular damage. Oxidative Med Cell Longev, 2017. 2017: p. 3172692, 1, 13

  38. Mercken EM, Mitchell SJ, Martin-Montalvo A, Minor RK, Almeida M, Gomes AP, Scheibye-Knudsen M, Palacios HH, Licata JJ, Zhang Y, Becker KG, Khraiwesh H, González-Reyes JA, Villalba JM, Baur JA, Elliott P, Westphal C, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R (2014) SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell 13(5):787–796

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Fukuoka T, Hattori K, Maruyama H, Hirayama M, Tanahashi N (2012) Laser-induced thrombus formation in mouse brain microvasculature: effect of clopidogrel. J Thromb Thrombolysis 34(2):193–198

    Article  PubMed  CAS  Google Scholar 

  40. Wang Y, Feng W, Xue W, Tan Y, Hein DW, Li XK, Cai L (2009) Inactivation of GSK-3beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes 58(6):1391–1402

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Wu H, Zhou S, Kong L, Chen J, Feng W, Cai J, Miao L, Tan Y (2014) Metallothionein deletion exacerbates intermittent hypoxia-induced renal injury in mice. Toxicol Lett 232(2):340–348

    Article  PubMed  CAS  Google Scholar 

  42. Chen Y, Wu Y, Gan X, Liu K, Lv X, Shen H, Dai G, Xu H (2016) Iridoid glycoside from Cornus officinalis ameliorated diabetes mellitus-induced testicular damage in male rats: involvement of suppression of the AGEs/RAGE/p38 MAPK signaling pathway. J Ethnopharmacol 194:850–860

    Article  PubMed  CAS  Google Scholar 

  43. Faid I, Al-Hussaini H, Kilarkaje N (2015) Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats. Toxicol Appl Pharmacol 289(3):482–494

    Article  PubMed  CAS  Google Scholar 

  44. Feyli SA, Ghanbari A, Keshtmand Z (2017) Therapeutic effect of pentoxifylline on reproductive parameters in diabetic male mice. Andrologia 49(1)

  45. Jiang X, Chen J, Zhang C, Zhang Z, Tan Y, Feng W, Skibba M, Xin Y, Cai L (2015) The protective effect of FGF21 on diabetes-induced male germ cell apoptosis is associated with up-regulated testicular AKT and AMPK/Sirt1/PGC-1alpha signaling. Endocrinology 156(3):1156–1170

    Article  PubMed  CAS  Google Scholar 

  46. Zhao L, Gu Q, Xiang L, Dong X, Li H, Ni J, Wan L, Cai G, Chen G (2017) Curcumin inhibits apoptosis by modulating Bax/Bcl-2 expression and alleviates oxidative stress in testes of streptozotocin-induced diabetic rats. Ther Clin Risk Manag 13:1099–1105

    Article  PubMed  PubMed Central  Google Scholar 

  47. Misso G et al (2014) Mir-34: a new weapon against cancer? Mol Ther Nucleic Acids 3:e194

    Article  PubMed  CAS  Google Scholar 

  48. Li N, Wang K, Li PF (2015) MicroRNA-34 family and its role in cardiovascular disease. Crit Rev Eukaryot Gene Expr 25(4):293–297

    Article  PubMed  Google Scholar 

  49. Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S, Kaluza D, Tréguer K, Carmona G, Bonauer A, Horrevoets AJG, Didier N, Girmatsion Z, Biliczki P, Ehrlich JR, Katus HA, Müller OJ, Potente M, Zeiher AM, Hermeking H, Dimmeler S (2013) MicroRNA-34a regulates cardiac ageing and function. Nature 495(7439):107–110

    Article  PubMed  CAS  Google Scholar 

  50. Ceriello A (2003) New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care 26(5):1589–1596

    Article  PubMed  CAS  Google Scholar 

  51. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058–1070

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Tan SM, de Haan JB (2014) Combating oxidative stress in diabetic complications with Nrf2 activators: how much is too much? Redox Rep 19(3):107–117

    Article  PubMed  CAS  Google Scholar 

  53. Lu H, Hao L, Li S, Lin S, Lv L, Chen Y, Cui H, Zi T, Chu X, Na L, Sun C (2016) Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway. Diabetologia 59(6):1247–1257

    Article  PubMed  CAS  Google Scholar 

  54. Rokavec M, Li H, Jiang L, Hermeking H (2014) The p53/miR-34 axis in development and disease. J Mol Cell Biol 6(3):214–230

    Article  PubMed  CAS  Google Scholar 

  55. Abdelali A, Al-Bader M, Kilarkaje N (2016) Effects of trans-resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis. Toxicol Appl Pharmacol 311:61–73

    Article  PubMed  CAS  Google Scholar 

  56. Cleary ML, Smith SD, Sklar J (1986) Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47(1):19–28

    Article  PubMed  CAS  Google Scholar 

  57. Tsujimoto Y, Finger L, Yunis J, Nowell P, Croce C (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226(4678):1097–1099

    Article  PubMed  CAS  Google Scholar 

  58. Castro RE, Ferreira DMS, Afonso MB, Borralho PM, Machado MV, Cortez-Pinto H, Rodrigues CMP (2013) miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol 58(1):119–125

    Article  PubMed  CAS  Google Scholar 

  59. Fang C, Qiu S, Sun F, Li W, Wang Z, Yue B, Wu X, Yan D (2017) Long non-coding RNA HNF1A-AS1 mediated repression of miR-34a/SIRT1/p53 feedback loop promotes the metastatic progression of colon cancer by functioning as a competing endogenous RNA. Cancer Lett 410:50–62

    Article  PubMed  CAS  Google Scholar 

  60. Lou G, Liu Y, Wu S, Xue J, Yang F, Fu H, Zheng M, Chen Z (2015) The p53/miR-34a/SIRT1 positive feedback loop in quercetin-induced apoptosis. Cell Physiol Biochem 35(6):2192–2202

    Article  PubMed  CAS  Google Scholar 

  61. Xia, C., et al., 0404 inhibits hepatocellular carcinoma through a p53/miR-34a/SIRT1 positive feedback loop. Sci Rep, 2017. 7(1): p. 4396

  62. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26(5):745–752

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z, Oren M (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26(5):731–743

    Article  PubMed  CAS  Google Scholar 

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Funding

This work was supported in part by the National Natural Science Foundation of China [81600573] and Norman Bethune Program of Jilin University [2015438] to Hao Wu; Natural Science Foundation of Jilin Province [20160101117JC and SCZSY201620] to Yonggang Wang; Natural Science Foundation of Jilin Province [2018SCZWSZX-045] to Ziping Jiang; and National Natural Science Foundation of China [81774393] to Zhaohui Wang.

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  1. Dan Jiao and Huan Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Ultrasound, China-Japan Union Hospital of Jilin University, 126 Xiantai St., Changchun, 130033, Jilin, China

    Dan Jiao

  2. Operating Theater, China-Japan Union Hospital of Jilin University, 126 Xiantai St., Changchun, 130033, Jilin, China

    Huan Zhang

  3. Department of Hand and Foot Surgery, The First Hospital of Jilin University, 71 Xinmin St., Changchun, 130021, Jilin, China

    Ziping Jiang & Hao Wu

  4. School of Science and Technology, Georgia Gwinnett College, Lawrenceville, GA, 30043, USA

    Wenlin Huang

  5. Center of Reproductive Medicine, Affiliated Hospital of Beihua University, 12 Jiefang Rd., Jilin, 132000, Jilin, China

    Zhuo Liu

  6. Department of Acupuncture and Tuina, Changchun University of Chinese Medicine, 1035 Boshuo Rd., Changchun, 130117, Jilin, China

    Zhaohui Wang

  7. Department of Urology, China-Japan Union Hospital of Jilin University, 126 Xiantai St.,, Changchun, 130033, Jilin, China

    Yonggang Wang

  8. Department of Translational Medicine, The First Hospital of Jilin University, 71 Xinmin St., Changchun, 130021, Jilin, China

    Hao Wu

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  1. Dan Jiao
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  2. Huan Zhang
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  8. Hao Wu
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Contributions

Hao Wu conceived the research. Hao Wu, Yonggang Wang, Dan Jiao, and Huan Zhang designed the experiments. Dan Jiao, Huan Zhang, Ziping Jiang, Wenlin Huang, Zhuo Liu, Zhaohui Wang, Yonggang Wang, and Hao Wu researched and interpreted data. Hao Wu, Yonggang Wang, Dan Jiao, and Huan Zhang wrote the manuscript. Dan Jiao, Huan Zhang, Ziping Jiang, Wenlin Huang, Zhuo Liu, Zhaohui Wang, Yonggang Wang, and Hao Wu reviewed and revised the manuscript. Hao Wu, Yonggang Wang, Ziping Jiang, and Zhaohui Wang provided funding. All the authors approve the version to be published.

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Correspondence to Yonggang Wang or Hao Wu.

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Jiao, D., Zhang, H., Jiang, Z. et al. MicroRNA-34a targets sirtuin 1 and leads to diabetes-induced testicular apoptotic cell death. J Mol Med 96, 939–949 (2018). https://doi.org/10.1007/s00109-018-1667-0

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