Skip to main content Accessibility help

MicroRNAs in acquired sensorineural hearing loss

  • H H R Chen (a1), P Wijesinghe (a1) (a2) and D A Nunez (a1) (a2)



This review summarises the current literature on the role of microRNAs in presbyacusis (age-related hearing loss) and sudden sensorineural hearing loss.


Medline, PubMed, Web of Science and Embase databases were searched for primary English-language studies, published between 2000 and 2017, which investigated the role of microRNAs in the pathogenesis of presbyacusis or sudden sensorineural hearing loss. Quality of evidence was assessed using the National Institutes of Health quality assessment tool.


Nine of 207 identified articles, 6 of good quality, satisfied the review's inclusion criteria. In presbyacusis, microRNAs in pro-apoptotic and autophagy pathways are upregulated, while microRNAs in proliferative and differentiation pathways are downregulated. Evidence for microRNAs having an aetiological role in sudden hearing loss is limited.


A shift in microRNA expression, leading to reduced cellular activity and impaired inner-ear homeostasis, may contribute to the pathogenesis of presbyacusis.


Corresponding author

Author for correspondence: Prof Desmond A Nunez, Division of Otolaryngology Head and Neck Surgery, Department of Surgery, University of British Columbia, Gordon and Leslie Diamond Health Care Centre, 4th Floor, 2775 Laurel Street, Vancouver, BC, Canada V5Z 1M9 E-mail: Fax: +1 604 875 5018


Hide All

Prof D A Nunez takes responsibility for the integrity of the content of the paper



Hide All
1Feder, K, Michaud, D, Ramage-Morin, P, McNamee, J, Beauregard, Y. Prevalence of hearing loss among Canadians aged 20 to 79: audiometric results from the 2012/2013 Canadian Health Measures Survey. Health Rep 2015;26:1825
2United Nations, Department of Economic and Social Affairs, Population Division. World Population Prospects: The 2017 Revision. New York: United Nations, 2017
3Schuknecht, HF, Gacek, MR. Cochlear pathology in presbycusis. Ann Otol Rhinol Laryngol 1993;102:116
4Gates, GA, Mills, JH. Presbycusis. Lancet 2005;366:1111–20
5Huang, Q, Tang, J. Age-related hearing loss or presbycusis. Eur Arch Otorhinolaryngol 2010;267:1179–91
6Stachler, RJ, Chandrasekhar, SS, Archer, SM, Rosenfeld, RM, Schwartz, SR, Barrs, DM et al. Clinical practice guideline: sudden hearing loss. Otolaryngol Head Neck Surg 2012;146:S135
7Alexander, TH, Harris, JP. Incidence of sudden sensorineural hearing loss. Otol Neurotol 2013;34:1586–9
8Nakashima, T, Sato, H, Gyo, K, Hato, N, Yoshida, T, Shimono, M et al. Idiopathic sudden sensorineural hearing loss in Japan. Acta Otolaryngol 2014;134:1158–63
9Suzuki, H, Tabata, T, Koizumi, H, Hohchi, N, Takeuchi, S, Kitamura, T et al. Prediction of hearing outcomes by multiple regression analysis in patients with idiopathic sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol 2014;123:821–5
10Mattox, DE, Simmons, FB. Natural history of sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol 1977;86:463–80
11Merchant, SN, Adams, JC, Nadol, JB Jr. Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss. Otol Neurotol 2005;26:151–60
12Rudnicki, A, Avraham, KB. MicroRNAs: the art of silencing in the ear. EMBO Mol Med 2012;4:849–59
13Pang, J, Xiong, H, Yang, H, Ou, Y, Xu, Y, Huang, Q et al. Circulating miR-34a levels correlate with age-related hearing loss in mice and humans. Exp Gerontol 2016;76:5867
14Liberati, A, Altman, DG, Tetzlaff, J, Mulrow, C, Gotzsche, PC, Ioannidis, JP et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62:e134
15National Heart, Lung, and Blood Institute. Study Quality Assessment Tools. In: [14 June 2019]
16Zhang, Q, Liu, H, McGee, J, Walsh, EJ, Soukup, GA, He, DZ. Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss. PloS One 2013;8:e62786
17Zhang, Q, Liu, H, Soukup, GA, He, DZ. Identifying microRNAs involved in aging of the lateral wall of the cochlear duct. PloS One 2014;9:e112857
18Huang, Q, Zheng, Y, Ou, Y, Xiong, H, Yang, H, Zhang, Z et al. MiR-34a/Bcl-2 signaling pathway contributes to age-related hearing loss by modulating hair cell apoptosis. Neurosci Lett 2017;661:51–6
19Pang, J, Xiong, H, Lin, P, Lai, L, Yang, H, Liu, Y et al. Activation of miR-34a impairs autophagic flux and promotes cochlear cell death via repressing ATG9A: implications for age-related hearing loss. Cell Death Dis 2017;8:e3079
20Xue, T, Wei, L, Zha, DJ, Qiu, JH, Chen, FQ, Qiao, L et al. MiR-29b overexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC-1alpha signaling: implications for age-related hearing loss. Int J Mol Med 2016;38:1387–94
21Xiong, H, Pang, J, Yang, H, Dai, M, Liu, Y, Ou, Y et al. Activation of miR-34a/SIRT1/p53 signaling contributes to cochlear hair cell apoptosis: implications for age-related hearing loss. Neurobiol Aging 2015;36:1692–701
22Li, Q, Peng, X, Huang, H, Li, J, Wang, F, Wang, J. RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss. Medicine (Baltimore) 2017;96:e8837
23Sekine, K, Matsumura, T, Takizawa, T, Kimura, Y, Saito, S, Shiiba, K et al. Expression profiling of microRNAs in the inner ear of elderly people by real-time PCR quantification. Audiol Neurootol 2017;22:135–45
24Su, Z, Yang, Z, Xu, Y, Chen, Y, Yu, Q. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget 2015;6:8474–90
25Tadros, SF, D'Souza, M, Zhu, X, Frisina, RD. Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea. Apoptosis 2008;13:1303–21
26Gross, A, McDonnell, JM, Korsmeyer, SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899–911
27Yamakuchi, M, Lowenstein, CJ. MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle 2009;8:712–15
28Welch, C, Chen, Y, Stallings, RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 2007;26:5017–22
29Someya, S, Yu, W, Hallows, WC, Xu, J, Vann, JM, Leeuwenburgh, C et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 2010;143:802–12
30Tan, M, Tang, C, Zhang, Y, Cheng, Y, Cai, L, Chen, X et al. SIRT1/PGC-1alpha signaling protects hepatocytes against mitochondrial oxidative stress induced by bile acids. Free Radic Res 2015;49:935–45
31Frucht, CS, Santos-Sacchi, J, Navaratnam, DS. MicroRNA181a plays a key role in hair cell regeneration in the avian auditory epithelium. Neurosci Lett 2011;493:44–8
32Sacheli, R, Nguyen, L, Borgs, L, Vandenbosch, R, Bodson, M, Lefebvre, P et al. Expression patterns of miR-96, miR-182 and miR-183 in the development inner ear. Gene Expr Patterns 2009;9:364–70
33Wang, XR, Zhang, XM, Du, J, Jiang, H. MicroRNA-182 regulates otocyst-derived cell differentiation and targets T-box1 gene. Hear Res 2012;286:5563
34Li, HQ, Kloosterman, W, Fekete, DM. MicroRNA-183 family members regulate sensorineural fates in the inner ear. J Neurosci 2010;30:3254–63
35Lewis, BP, Burge, CB, Bartel, DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120:1520
36Mencia, A, Modamio-Hoybjor, S, Redshaw, N, Morin, M, Mayo-Merino, F, Olavarrieta, L et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet 2009;41:609–13
37Lewis, MA, Quint, E, Glazier, AM, Fuchs, H, De Angelis, MH, Langford, C et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet 2009;41:614–18
38Solda, G, Robusto, M, Primignani, P, Castorina, P, Benzoni, E, Cesarani, A et al. A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing. Hum Mol Genet 2012;21:577–85
39Tai, H, Wang, Z, Gong, H, Han, X, Zhou, J, Wang, X et al. Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence. Autophagy 2017;13:99113
40Huang, J, Sun, W, Huang, H, Ye, J, Pan, W, Zhong, Y et al. MiR-34a modulates angiotensin II-induced myocardial hypertrophy by direct inhibition of ATG9A expression and autophagic activity. PloS One 2014;9:e94382
41Chang, J, Davis-Dusenbery, BN, Kashima, R, Jiang, X, Marathe, N, Sessa, R et al. Acetylation of p53 stimulates miRNA processing and determines cell survival following genotoxic stress. EMBO J 2013;32:3192–205
42Lewis, MA, Buniello, A, Hilton, JM, Zhu, F, Zhang, WI, Evans, S et al. Exploring regulatory networks of miR-96 in the developing inner ear. Sci Rep 2016;6:23363
43Tong, B, Hornak, AJ, Maison, SF, Ohlemiller, KK, Liberman, MC, Simmons, DD. Oncomodulin, an EF-hand Ca2+ buffer, is critical for maintaining cochlear function in mice. J Neurosci 2016;36:1631–5
44Tra, Y, Frisina, RD, D'Souza, M. A novel high-throughput analysis approach: immune response-related genes are upregulated in age-related hearing loss. Open Access Bioinformatics 2011;3:107–22
45Niceta, M, Stellacci, E, Gripp, KW, Zampino, G, Kousi, M, Anselmi, M et al. Mutations impairing GSK3-mediated MAF phosphorylation cause cataract, deafness, intellectual disability, seizures, and a down syndrome-like facies. Am J Hum Genet 2015;96:816–25
46Ohlemiller, KK, Rosen, AD, Gagnon, PM. A major effect QTL on chromosome 18 for noise injury to the mouse cochlear lateral wall. Hear Res 2010;260:4753
47Hedlund, M, Tangvoranuntakul, P, Takematsu, H, Long, JM, Housley, GD, Kozutsumi, Y et al. N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol 2007;27:4340–6
48Han, SY, Kim, S, Shin, DH, Cho, JH, Nam, SI. The expression of AGO2 and DGCR8 in idiopathic sudden sensorineural hearing loss. Clin Exp Otorhinolaryngol 2014;7:269–74
49Kim, S, Lee, JH, Nam, SI. Dicer is down-regulated and correlated with Drosha in idiopathic sudden sensorineural hearing loss. J Korean Med Sci 2015;30:1183–8
50Kobayashi, H, Tomari, Y. RISC assembly: coordination between small RNAs and Argonaute proteins. Biochim Biophys Acta 2016;1859:7181
51Lee, Y, Ahn, C, Han, J, Choi, H, Kim, J, Yim, J et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003;425:415–19
52Bernstein, E, Kim, SY, Carmell, MA, Murchison, EP, Alcorn, H, Li, MZ et al. Dicer is essential for mouse development. Nat Genet 2003;35:215–17
53Friedman, LM, Avraham, KB. MicroRNAs and epigenetic regulation in the mammalian inner ear: implications for deafness. Mamm Genome 2009;20:581603
54Sand, M, Skrygan, M, Georgas, D, Arenz, C, Gambichler, T, Sand, D et al. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinog 2012;51:916–22



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed