Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis

Age-related hearing loss (ARHL) is a gradual, symmetrical sensorineural disorder. Exploring the pathogenesis of ARHL from a biological perspective is important for its treatment. In this study, we analyzed the circRNA expression profiles of 2-month-old miR-29a+/+ mice and miR-29a−/− mice by transcri...

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Main Authors: Mulan Li, Bingqian Li, Shuli Wang, Pengcheng Liu, Zhen Liu, Tihua Zheng, Ruishuang Geng, Bo Li, Qingyin Zheng, Peng Ma
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Experimental Gerontology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0531556525000877
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author Mulan Li
Bingqian Li
Shuli Wang
Pengcheng Liu
Zhen Liu
Tihua Zheng
Ruishuang Geng
Bo Li
Qingyin Zheng
Peng Ma
author_facet Mulan Li
Bingqian Li
Shuli Wang
Pengcheng Liu
Zhen Liu
Tihua Zheng
Ruishuang Geng
Bo Li
Qingyin Zheng
Peng Ma
author_sort Mulan Li
collection DOAJ
description Age-related hearing loss (ARHL) is a gradual, symmetrical sensorineural disorder. Exploring the pathogenesis of ARHL from a biological perspective is important for its treatment. In this study, we analyzed the circRNA expression profiles of 2-month-old miR-29a+/+ mice and miR-29a−/− mice by transcriptome sequencing to investigate the role of circRNAs in ARHL. We identified 12 differentially expressed circRNAs in the two groups. Our focus was on circRNAs predicted to regulate miR-29a, with novel_circ_0004013 identified as having a targeted binding relationship with miR-29a-3p. Dual luciferase assays confirmed that miR-29a-3p is a direct target of novel_circ_0004013. Fluorescence in situ hybridization (FISH) was employed to localize the novel_circ_0004013 in HEI-OC1 cells and the cochlea. Novel_circ_0004013 was mainly expressed in the cytoplasm. In the hair cells (HCs) and stria vascularis (SV) regions of miR-29a−/− mice, novel_circ_0004013 expression was higher than the corresponding regions in miR-29a+/+ mice. Furthermore, Western blot assays revealed that levels of oxidative stress and apoptosis were significantly decreased in HEI-OC1 cells following the knockdown of novel_circ_0004013, whereas these levels were significantly increased in HEI-OC1 cells after the knockdown of miR-29a-3p. It was indicated in rescue assays that novel_circ_0004013 expedited oxidative stress and apoptosis of HEI-OC1 cells via modulation on miR-29a-3p. These findings may reveal the important role of novel_circ_0004013 in hearing loss and provide a new perspective and theoretical basis for the molecular mechanism of ARHL.
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institution Kabale University
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language English
publishDate 2025-06-01
publisher Elsevier
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series Experimental Gerontology
spelling doaj-art-6a3b0cc72d0a41c8a3e1950d01853a332025-08-20T03:52:43ZengElsevierExperimental Gerontology1873-68152025-06-0120511275810.1016/j.exger.2025.112758Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysisMulan Li0Bingqian Li1Shuli Wang2Pengcheng Liu3Zhen Liu4Tihua Zheng5Ruishuang Geng6Bo Li7Qingyin Zheng8Peng Ma9Hearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, ChinaHearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, China; Department of Medical Genetics and Cell Biology, Binzhou Medical University, Yantai, China; Corresponding author at: Hearing and Speech Rehabilitation Institute, School of Special Education and Rehabilitation, Binzhou Medical University, Yantai, China.Age-related hearing loss (ARHL) is a gradual, symmetrical sensorineural disorder. Exploring the pathogenesis of ARHL from a biological perspective is important for its treatment. In this study, we analyzed the circRNA expression profiles of 2-month-old miR-29a+/+ mice and miR-29a−/− mice by transcriptome sequencing to investigate the role of circRNAs in ARHL. We identified 12 differentially expressed circRNAs in the two groups. Our focus was on circRNAs predicted to regulate miR-29a, with novel_circ_0004013 identified as having a targeted binding relationship with miR-29a-3p. Dual luciferase assays confirmed that miR-29a-3p is a direct target of novel_circ_0004013. Fluorescence in situ hybridization (FISH) was employed to localize the novel_circ_0004013 in HEI-OC1 cells and the cochlea. Novel_circ_0004013 was mainly expressed in the cytoplasm. In the hair cells (HCs) and stria vascularis (SV) regions of miR-29a−/− mice, novel_circ_0004013 expression was higher than the corresponding regions in miR-29a+/+ mice. Furthermore, Western blot assays revealed that levels of oxidative stress and apoptosis were significantly decreased in HEI-OC1 cells following the knockdown of novel_circ_0004013, whereas these levels were significantly increased in HEI-OC1 cells after the knockdown of miR-29a-3p. It was indicated in rescue assays that novel_circ_0004013 expedited oxidative stress and apoptosis of HEI-OC1 cells via modulation on miR-29a-3p. These findings may reveal the important role of novel_circ_0004013 in hearing loss and provide a new perspective and theoretical basis for the molecular mechanism of ARHL.http://www.sciencedirect.com/science/article/pii/S0531556525000877RNA-seqcircRNAmiR-29aAge-related hearing loss
spellingShingle Mulan Li
Bingqian Li
Shuli Wang
Pengcheng Liu
Zhen Liu
Tihua Zheng
Ruishuang Geng
Bo Li
Qingyin Zheng
Peng Ma
Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis
Experimental Gerontology
RNA-seq
circRNA
miR-29a
Age-related hearing loss
title Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis
title_full Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis
title_fullStr Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis
title_full_unstemmed Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis
title_short Novel_circ_0004013 targeting miR-29a-3p affects age-related hearing loss in miR-29a mouse model by RNA-seq analysis
title_sort novel circ 0004013 targeting mir 29a 3p affects age related hearing loss in mir 29a mouse model by rna seq analysis
topic RNA-seq
circRNA
miR-29a
Age-related hearing loss
url http://www.sciencedirect.com/science/article/pii/S0531556525000877
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