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Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to occupational noise

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Abstract

Genetic factors play an important role in susceptibility to noise-induced hearing loss (NIHL). Alternative splicing (AS) is an essential mechanism affecting gene expression associated with disease pathogenesis at the post-transcriptional level, but has rarely been studied in NIHL. To explore the role of AS in the development of NIHL, we performed a comprehensive analysis of RNA splicing alterations by comparing the RNA-seq data from blood samples from NIHL patients and subjects with normal hearing who were exposed to the same noise environment. A total of 356 differentially expressed genes, including 23 transcription factors, were identified between the two groups. Of particular note was the identification of 56 aberrant alternative splicing events generated by 41 differentially expressed genes between the two groups, with exon skip** events accounting for 54% of all the differentially alternative splicing (DAS) events. The results of functional enrichment analysis showed that these intersecting DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways. Together, our findings provide insights into the role of AS events in susceptibility and pathogenesis of NIHL.

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The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

References

  • Böttger EC, Schacht J (2013) The mitochondrion: a perpetrator of acquired hearing loss. Hear Res 303:12–19

    Article  Google Scholar 

  • Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H (2013) The Parkinson’s disease–linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci 16(9):1257–1265

    Article  CAS  Google Scholar 

  • Chen J, Ma P, Yuan H, Wang W, Lu P, Ding X, Lun Y, Yang Q, Lu L (2022) mito-TEMPO attenuates oxidative stress and mitochondrial dysfunction in noise-induced hearing loss via maintaining TFAM-mtDNA interaction and mitochondrial biogenesis. Front Cell Neurosci 16:803718

  • Fetoni AR, De Bartolo P, Eramo SL, Rolesi R, Paciello F, Bergamini C, Fato R, Paludetti G, Petrosini L, Troiani D (2013) Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense. J Neurosci 33(9):4011–4023

    Article  CAS  Google Scholar 

  • Friedman DJ, Pollak MR (2020) APOL1 and kidney disease: from genetics to biology. Annu Rev Physiol 82:323–342

    Article  CAS  Google Scholar 

  • Guo L, Cao W, Niu Y, He S, Chai R, Yang J (2021) Autophagy regulates the survival of hair cells and spiral ganglion neurons in cases of noise, ototoxic drug, and age-induced sensorineural hearing loss. Front Cell Neurosci 15:760422

  • Hu N, Rutherford MA, Green SH (2020) Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca(2+)-permeable AMPA receptors. Proc Natl Acad Sci U S A 117(7):3828–3838

    Article  CAS  Google Scholar 

  • Jiang Z, Wang J, Feng Y, Sun D, Zhang X, Shi H, Wang J, Salvi R, Wang H, Yin S (2021) Analysis of early biomarkers associated with noise-induced hearing loss among shipyard workers. JAMA Netw Open 4(9):e2124100

    Article  Google Scholar 

  • Kurabi A, Keithley EM, Housley GD, Ryan AF, Wong ACY (2017) Cellular mechanisms of noise-induced hearing loss. Hear Res 349:129–137

    Article  CAS  Google Scholar 

  • Le Prell CG, Hammill TL, Murphy WJ (2019) Noise-induced hearing loss and its prevention: integration of data from animal models and human clinical trials. J Acoust Soc Am 146(5):4051–4074

    Article  Google Scholar 

  • Li Y, Li S, Wu L, Wu T, Li M, Du D, Chen Y, Wang C, Li X, Zhang S, Zhao Z, Zheng L, Chen M, Li M, Li T, Shi X, Qiao Y (2023) Sestrin 2 deficiency exacerbates noise-induced cochlear injury through inhibiting ULK1/Parkin-mediated mitophagy. Antioxid Redox Signal 38(1–3):115–136

    Article  CAS  Google Scholar 

  • Li P, Bing D, Wang S, Chen J, Du Z, Sun Y, Qi F, Zhang Y, Chu H (2019) Sleep deprivation modifies noise-induced cochlear injury related to the stress hormone and autophagy in female mice. Front Neurosci 13:1297

  • Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15(12):550

  • Lu G, Tan H, Schmauck-Medina T, Wang L, Chen J, Cho YL, Chen K, Zhang JZ, He W, Wu Y, **a D, Zhou J, Fang EF, Fang L, Liu W, Shen HM (2022) WIPI2 positively regulates mitophagy by promoting mitochondrial recruitment of VCP. Autophagy 18(12):2865–2879

    Article  CAS  Google Scholar 

  • Minami SB, Yamashita D, Schacht J, Miller JM (2004) Calcineurin activation contributes to noise-induced hearing loss. J Neurosci Res 78(3):383–392

    Article  CAS  Google Scholar 

  • Nakano Y, Kelly MC, Rehman AU, Boger ET, Morell RJ, Kelley MW, Friedman TB, Bánfi B (2018) Defects in the alternative splicing-dependent regulation of REST cause deafness. Cell 174(3):536-548.e21

    Article  CAS  Google Scholar 

  • Natarajan N, Batts S, Stankovic KM (2023) Noise-induced hearing loss. J Clin Med 12(6):2347

    Article  CAS  Google Scholar 

  • Nicotera TM, Hu BH, Henderson D (2003) The caspase pathway in noise-induced apoptosis of the chinchilla cochlea. JARO - J Assoc Res Otolaryngol 4(4):466–477

    Article  Google Scholar 

  • Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40(12):1413–1415

    Article  CAS  Google Scholar 

  • Pickles S, Vigié P, Youle RJ (2018) Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol 28(4):R170–R185

    Article  CAS  Google Scholar 

  • Siemens J, Lillo C, Dumont RA, Reynolds A, Williams DS, Gillespie PG, Müller U (2004) Cadherin 23 is a component of the tip link in hair-cell stereocilia. Nature 428(6986):950–955

    Article  CAS  Google Scholar 

  • WHO (2021) World report on hearing. https://www.who.int/publications/i/item/world-report-on-hearing

  • Wright CJ, Smith C, Jiggins CD (2022) Alternative splicing as a source of phenotypic diversity. Nat Rev Genet 23(11):697–710

    Article  CAS  Google Scholar 

  • Xu T, Nie L, Zhang Y, Mo J, Feng W, Wei D, Petrov E, Calisto LE, Kachar B, Beisel KW, Vazquez AE, Yamoah EN (2007) Roles of alternative splicing in the functional properties of inner ear-specific KCNQ4 channels. J Biol Chem 282(33):23899–23909

    Article  CAS  Google Scholar 

  • Ye B, Fan C, Shen Y, Wang Q, Hu H, **ang M (2019) The antioxidative role of autophagy in hearing loss. Front Neurosci 12:1010

  • Yu L, Chen Y, Tooze SA (2017) Autophagy pathway: cellular and molecular mechanisms. Autophagy 14(2):207–215

    Article  Google Scholar 

  • Yuan H, Wang X, Hill K, Chen J, Lemasters J, Yang SM, Sha SH (2015) Autophagy attenuates noise-induced hearing loss by reducing oxidative stress. Antioxid Redox Signal 22(15):1308–1324

    Article  CAS  Google Scholar 

  • Zhang G, Zheng H, Pyykko I, Zou J (2019) The TLR-4/NF-κB signaling pathway activation in cochlear inflammation of rats with noise-induced hearing loss. Hear Res 379:59–68

    Article  CAS  Google Scholar 

  • Zhaorigetu S, Wan G, Kaini R, Jiang Z, Hu CA (2008) ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death. Autophagy 4(8):1079–1082

    Article  CAS  Google Scholar 

  • Zheng HW, Chen J, Sha SH (2014) Receptor-interacting protein kinases modulate noise-induced sensory hair cell death. Cell Death Dis 5:e1262

    Article  CAS  Google Scholar 

  • Zhong Y, Li J, Ye M, ** X (2023) The characteristics of FBXO7 and its role in human diseases. Gene 851:146972

    Article  CAS  Google Scholar 

  • Zhou J, Shi Z, Zhou L, Hu Y, Zhang M (2020) Occupational noise-induced hearing loss in China: a systematic review and meta-analysis. BMJ Open 10(9):e039576

    Article  Google Scholar 

  • Zhou Z, Yu X, Jiang B, Feng W, Tian Y, Liu Z, Wang J, Huang P (2021) Alternative splicing of three genes encoding mechanotransduction-complex proteins in auditory hair cells. eNeuro 8(1):ENEURO.0381-20.2020

  • Zhu Y, Zhao L, Liu L, Gao P, Tian W, Wang X, ** H, Xu H, Chen Q (2010) Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis. Protein Cell 1(5):468–477

    Article  CAS  Google Scholar 

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Funding

This work was supported by the Military Logistics Research Project (18CXZ015).

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Author notes

  1. Jia-Wei Chen and Jun-Jie Shao contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Fourth Military Medical University, **’an, China

    Jia-Wei Chen, Pei-Heng Lu, Si-Yu Li, Hao Yuan, Peng-Wei Ma, Yu-Qiang Lun, Wei-Long Wang, Rui Liang, Wei Gao & Lian-Jun Lu

  2. Department of Otolaryngology Head and Neck Surgery, the Air Force Hospital From Eastern Theater of PLA, Nan**g, China

    Jia-Wei Chen

  3. Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, **’an, China

    Jun-Jie Shao, Shao-Fei Zhao & Qian Yang

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  1. Jia-Wei Chen
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Contributions

Conceptualization, L-J. L. and Q. Y.; methodology, J-W. C. and J-J. S.; software, J-J. S. and S-F. Z.; validation, J-W. C., J-J. S., and S-Y. L.; formal analysis J-W. C. and J-J. S.; investigation, H. Y., P–H. L., and P-W. M.; resources, J-W. C., Y-Q. L., W-L. W., and R. L.; writing—original draft preparation, J-W. C. and J-J. S.; writing—review and editing, L-J. L. and Q. Y.; visualization, J-W. C., J-J. S., S-F. Z., and S-Y. L.; supervision, W. G.; project administration, L-J. L. and Q. Y.; funding acquisition, L-J. L. All the authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Lian-Jun Lu.

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Ethics approval

This study was conducted in accordance with the Declaration of Helsinki and approved by the Bioethics Committee of Tangdu Hospital of Air Force Military Medical University (No. 201912–11, 2019/12/30).

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Informed consent was obtained from all the subjects involved in the study.

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Consent was given by all the authors.

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The authors declare no competing interests.

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Responsible Editor: Lotfi Aleya

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Qian Yang and Lian-Jun Lu are co-senior authors of the study.

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Chen, JW., Shao, JJ., Zhao, SF. et al. Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to occupational noise. Environ Sci Pollut Res 30, 107993–108004 (2023). https://doi.org/10.1007/s11356-023-29981-w

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