title: Circulating miR-34a levels correlate with age-related hearing loss in mice and humans.
abstract: Age-related hearing loss (AHL) is a progressive neurodegenerative disease that is largely silent in its initial stages. There is no sensitive blood biomarker for diagnosis or early detection of AHL. MicroRNAs (miRNAs or miRs) are abundant and highly stable in blood, and have been recently described as powerful circulating biomarkers in a wide range of diseases. In the present study, we identified concordant increases in miR-34a levels in the cochlea, auditory cortex, and plasma of C57BL/6 mice during aging. These increases were accompanied by elevated hearing thresholds and greater loss of hair cells. Levels of miR-34a targets, silent information regulator 1 (SIRT1), B-cell lymphoma-2 (Bcl-2), and E2F transcription factor 3 (E2F3), in the cochlea, auditory cortex, and plasma decreased with aging inversely to miR-34a. Moreover, plasma miR-34a levels were significantly higher in patients with AHL compared with controls who had normal hearing and had a receiver-operating characteristic curve that distinguished AHL patients from controls. However, SIRT1, Bcl-2, and E2F3 showed no correlation with AHL in humans. In summary, circulating miR-34a level may potentially serve as a useful biomarker for early detection of AHL.
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Pang
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Haidi
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Suijun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China. Electronic address: yiqingzheng@hotmail.com.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000367:Age Factors; D000818:Animals; D019540:Area Under Curve; D001301:Audiometry, Pure-Tone; D001303:Auditory Cortex / Q000378:metabolism / Q000503:physiopathology; D001309:Auditory Threshold; D016022:Case-Control Studies; D003051:Cochlea / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006198:Hair Cells, Auditory / Q000378:metabolism; D006309:Hearing / Q000235:genetics*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011304:Presbycusis / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; C522425:MIRN34 microRNA, human; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs
keywords: Biomarker; MicroRNA; Plasma; Presbycusis