Research Paper Volume 12, Issue 8 pp 7491—7510

RNA-seq analysis of potential lncRNAs for age-related hearing loss in a mouse model

Tong Zhao 1, *, , Xiuzhen Liu 2, *, , Zehua Sun 1, *, , Jinjin Zhang 1, , Xiaolin Zhang 3, , Chaoyun Wang 1, , Ruishuang Geng 1, , Tihua Zheng 1, , Bo Li 1, , Qing Yin Zheng 4, ,

  • 1 Hearing and Speech Rehabilitation Institute, Binzhou Medical University, Yantai, China
  • 2 Clinical Medicine Laboratory, Binzhou Medical University Hospital, Binzhou, China
  • 3 Department of Otolaryngology-Head and Neck Surgery, Binzhou Medical University Hospital, Binzhou, China
  • 4 Department of Otolaryngology- Head and Neck Surgery, Case Western Reserve University, Cleveland, USA
* Equal contribution

received: September 6, 2019 ; accepted: March 2, 2020 ; published: April 26, 2020 ;

https://doi.org/10.18632/aging.103103
How to Cite

Copyright © 2020 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Age-related hearing loss (AHL) is an important health problem in the elderly population. Its molecular mechanisms have not been fully elucidated. In this study, we analyzed the differential expression of lncRNAs and mRNAs in the cochleae of six-week-old and one-year-old C57BL/6J mice through RNA-seq analysis. We found 738 and 2033 differentially expressed lncRNAs and mRNAs, respectively, in these two groups (corrected P < 0.05). We focused on the intersection of known genes associated with hearing loss and differentially expressed mRNAs in RNA-seq. There are 34 mRNAs in this intersection, which include all 29 mRNAs enriched in the sensory perception of sound (GO: 0007605). We selected 11 lncRNAs that are predicted to regulate the 34 mRNAs to validate their expression levels in animal and cellular models of AHL by qRT-PCR. Among these lncRNAs, four were significantly different in both animal and cellular models of AHL, and the lncRNA NONMMUT010961.2 was the most markedly different. Knocking down lncRNA NONMMUT010961.2, we found the expression of oxidative stress and apoptosis-related gene Ar and hearing loss-related gene Hgf is significantly reduced in HEI-OC1 cells. Our results suggest that lncRNAs NONMMUT010961.2 may be associated with AHL and may thus lead to a new treatment for AHL.

Abbreviations

AHL: Age-related hearing loss; lncRNAs: long noncoding RNAs; miRNAs: microRNAs; ncRNAs: non-coding RNAs; qRT-PCR: Quantitative real-time polymerase chain reaction; ROS: promoted reactive oxygen species; Nrf2: nuclear factor like (erythroid-derived 2); GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO-BP: Gene ontology- biological process; CCK-8: Cell Counting Kit-8; RTCA: Real-Time Cell Analyzer; HO-1: heme oxygenase-1; H2O2: Hydrogen peroxide.