The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma

Abstract

Acoustic trauma, one of the leading causes of sensorineural hearing loss, induces sensory hair cell damage in the cochlea. Identifying the molecular mechanisms involved in regulating sensory hair cell death is critical towards developing effective treatments for preventing hair cell damage. Recently, microRNAs (miRNAs) have been shown to participate in the regulatory mechanisms of inner ear development and homeostasis. However, their involvement in cochlear sensory cell degeneration following acoustic trauma is unknown. Here, we profiled the expression pattern of miRNAs in the cochlear sensory epithelium, defined miRNA responses to acoustic overstimulation, and explored potential mRNA targets of miRNAs that may be responsible for the stress responses of the cochlea. Expression analysis of miRNAs in the cochlear sensory epithelium revealed constitutive expression of 176 miRNAs, many of which have not been previously reported in cochlear tissue. Exposure to intense noise caused significant threshold shift and apoptotic activity in the cochleae. Gene expression analysis of noise-traumatized cochleae revealed time-dependent transcriptional changes in the expression of miRNAs. Target prediction analysis revealed potential target genes of the significantly downregulated miRNAs, many of which had cell death- and apoptosis-related functions. Verification of the predicted targets revealed a significant upregulation of Taok1, a target of miRNA-183. Moreover, inhibition of miR-183 with morpholino antisense oligos in cochlear organotypic cultures revealed a negative correlation between the expression levels of miR-183 and Taok1, suggesting the presence of a miR-183/Taok1 target pair. Together, miRNA profiling as well as the target analysis and validation suggest the involvement of miRNAs in the regulation of the degenerative process of the cochlea following acoustic overstimulation. The miR-183/Taok1 target pair is likely to play a role in this regulatory process.

MiR-183 Regulates ITGB1P Expression and Promotes Invasion of Endometrial Stromal Cells

“…Moreover, it has been reported that miR-183 is upregulated in colorectal cancer, prostate cancer, and hepatocellular carcinomas and downregulated in ovarian cancer, breast cancer stem cells, and osteosarcomas, pointing to varied and cell type-dependent function of miR-183. Several target genes of miR-183 including ITGB1, Taok1, Ezrin, EGR1, PDCD4, and LRP6 have been identified and validated [ 13 – 19 ].…”

The Diverse Roles of TAO Kinases in Health and Diseases

“…Jing et al [ 69 ] showed that miR-381-3p promoted chondrogenesis in umbilical cord mesenchymal stem cells through direct suppression of TAOK1 and the downstream Hippo signaling pathway, indicating that TAOK1 may regulate chondrogenesis via the Hippo cascade. In an acoustic trauma study by Patel et al [ 70 ], the downregulation of miRNA-183 and upregulation of TAOK1 were observed in noise-traumatized cochlear cells in rats, indicating that the miR-183/TAOK1 pathway is likely to play a role in sensorineural hearing loss.…”

Mechanisms of sensorineural cell damage, death and survival in the cochlea

“…In animals exposed to intense noise, MAPK phosphorylation in the cochlea is altered, ERK1/2 in the sensory and support cells of the cochlear sensory epithelium are activated by phosphorylation; while JNK and p38 MAPKs showed late activation in the SGN, de novo syntheses of the MAPKs are also observed (Meltser et al, 2010 ; Jamesdaniel et al, 2011 ; Maeda et al, 2013 ; Patel et al, 2013 ). Radiation therapy for the treatment of head and neck cancers produces severe ototoxicity due to the increased production of ROS.…”