Combined Bioinformatic Analysis and RNA Sequencing Uncover Key Tinnitus-Related Molecules in the Cingulate Gyrus.
- 1Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
- 2Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract
Tinnitus arises from maladaptive plasticity and abnormal synaptic function, not only in auditory pathways but also in limbic regions. Among these, the cingulate gyrus plays a pivotal part in shaping the emotional burden and sensory filtering disturbances often seen in tinnitus patients. Yet, the specific molecular players operating within this region remain poorly understood, and most existing bioinformatic predictions have not been tested in living systems. Here, we combined multi-database mining with in vivo transcriptomic profiling to identify and validate key proteins and pathways linked to tinnitus in the cingulate gyrus. We built and compared protein-protein interaction networks representing auditory perception, acoustic challenge, and tinnitus states, thereby pinning down candidate hub molecules. To verify these candidates, we used a noise-induced mouse model of tinnitus, confirmed the phenotype via gap prepulse inhibition of acoustic startle (GPIAS), and then performed RNA-seq and qPCR on cingulate gyrus tissue. The bioinformatic screens pointed to AKT1 and TNF as central hubs, suggestive of an inflammatory-survival signaling axis. In our animal experiments, RNA-seq showed a clear rise in Akt1 transcript levels in the tinnitus group, and functional enrichment analysis pointed to marked changes in extracellular matrix organization, cell adhesion, and cytokine receptor pathways. qPCR further corroborated the Akt1 upregulation. Taken together, our integrative strategy establishes AKT1 and TNF as topologically central hub proteins in the cingulate gyrus tinnitus network, and validates Akt1 upregulation in vivo, offering potential biomarker candidates and therapeutic leads for future studies.
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BibTeX
@article{jin2026combined,
title = {{Combined Bioinformatic Analysis and RNA Sequencing Uncover Key Tinnitus-Related Molecules in the Cingulate Gyrus.}},
author = {Yuan Jin and Xinyu Shi and Qiong Zhang and Bei Guo and Ying Xiong and Yao Hu and Haixia He and Pei Gao and Wei Chen},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198543},
url = {https://europepmc.org/article/MED/42883790},
note = {CC BY},
}
RIS
TY - JOUR
TI - Combined Bioinformatic Analysis and RNA Sequencing Uncover Key Tinnitus-Related Molecules in the Cingulate Gyrus.
AU - Yuan Jin
AU - Xinyu Shi
AU - Qiong Zhang
AU - Bei Guo
AU - Ying Xiong
AU - Yao Hu
AU - Haixia He
AU - Pei Gao
AU - Wei Chen
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198543
UR - https://europepmc.org/article/MED/42883790
AB - Tinnitus arises from maladaptive plasticity and abnormal synaptic function, not only in auditory pathways but also in limbic regions. Among these, the cingulate gyrus plays a pivotal part in shaping the emotional burden and sensory filtering disturbances often seen in tinnitus patients. Yet, the specific molecular players operating within this region remain poorly understood, and most existing bioinformatic predictions have not been tested in living systems. Here, we combined multi-database mining with in vivo transcriptomic profiling to identify and validate key proteins and pathways linked to tinnitus in the cingulate gyrus. We built and compared protein-protein interaction networks representing auditory perception, acoustic challenge, and tinnitus states, thereby pinning down candidate hub molecules. To verify these candidates, we used a noise-induced mouse model of tinnitus, confirmed the phenotype via gap prepulse inhibition of acoustic startle (GPIAS), and then performed RNA-seq and qPCR on cingulate gyrus tissue. The bioinformatic screens pointed to AKT1 and TNF as central hubs, suggestive of an inflammatory-survival signaling axis. In our animal experiments, RNA-seq showed a clear rise in Akt1 transcript levels in the tinnitus group, and functional enrichment analysis pointed to marked changes in extracellular matrix organization, cell adhesion, and cytokine receptor pathways. qPCR further corroborated the Akt1 upregulation. Taken together, our integrative strategy establishes AKT1 and TNF as topologically central hub proteins in the cingulate gyrus tinnitus network, and validates Akt1 upregulation in vivo, offering potential biomarker candidates and therapeutic leads for future studies.
SN - 1422-0067
ER -