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RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss.

ABSTRACT: This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expressed microRNAs (DEMs). The target genes of the DEMs were predicted using the online tool miRWalk, which were then mapped to DAVID (https://david.ncifcrf.gov/) for functional annotation based on GO database and for pathway enrichment analysis based on KEGG. Finally, a miRNA-target-protein-protein interaction (PPIs) network was constructed using the DEMs and their target genes with interaction.Differential expression analysis reveals 24 DEMs between the SSNHL group and control group. A total of 1083 target genes were predicted. GO functional annotation analysis reveals that the target genes in the top 10 terms are mainly related to the development of salivary glands, neurotransmission, dendritic development, and other processes. KEGG pathway enrichment analysis reveals that the target genes were functionally enriched in pathways arachidonic acid metabolism, complement and coagulation cascades, linoleic acid metabolism, and MAPK signaling pathway. In the miRNA-target-PPI network, hsa-miR-34a/548n/15a/143/23a/210/1255a/18b/ /1180/99b had the most target genes; genes YWHAG, GSK3B, CDC42, NR3C1, LCK, UNC119, SIN3A, and NFKB2, interact with most other genes among all the predicted target genes.Hsa-miR-34a/15a/23a/210/18b/548n/143 is likely to have a role in the pathogenesis of SSNHL.

SUBMITTER: Li Q

PROVIDER: S-EPMC5708990 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss.

Li Qi Q Peng Xiaohong X Huang Haoran H Li Jingjing J Wang Fan F Wang Jie J

Medicine 20171101 47

This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expre ...[more]

PMID: 29381991

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Project description:IntroductionTo compare inpatient treated patients with idiopathic (ISSNHL) and non-idiopathic sudden sensorineural hearing loss (NISSNHL) regarding frequency, hearing loss, treatment and outcome.MethodsAll 574 inpatient patients (51% male, median age: 60 years) with ISSNHL and NISSNHL, who were treated in federal state Thuringia in 2011 and 2012, were included retrospectively. Univariate and multivariate statistical analyses were performed.ResultsISSNHL was diagnosed in 490 patients (85%), NISSNHL in 84 patients (15%). 49% of these cases had hearing loss due to acute otitis media, 37% through varicella-zoster infection or Lyme disease, 10% through Menière disease and 7% due to other reasons. Patients with ISSNHL and NISSNHL showed no difference between age, gender, side of hearing loss, presence of tinnitus or vertigo and their comorbidities. 45% of patients with ISSNHL and 62% with NISSNHL had an outpatient treatment prior to inpatient treatment (p < 0.001). The mean interval between onset of hearing loss to inpatient treatment was shorter in ISSNHL (7.7 days) than in NISSNHL (8.9 days; p = 0.02). The initial hearing loss of the three most affected frequencies in pure-tone average (3PTAmax) scaled 72.9 dBHL ± 31.3 dBHL in ISSNHL and 67.4 dBHL ± 30.5 dBHL in NISSNHL. In the case of acute otitis media, 3PTAmax (59.7 dBHL ± 24.6 dBHL) was lower than in the case of varicella-zoster infection or Lyme disease (80.11 dBHL ± 34.19 dBHL; p = 0.015). Mean absolute hearing gain (Δ3PTAmaxabs) was 8.1 dB ± 18.8 dB in patients with ISSNHL, and not different in NISSNHL patients with 10.2 dB ± 17.6 dB. A Δ3PTAmaxabs ≥ 10 dB was reached in 34.3% of the patients with ISSNHL and to a significantly higher rate of 48.8% in NISSNHL patients (p = 0.011).ConclusionsISSNHL and NISSNHL show no relevant baseline differences. ISSNHL tends to have a higher initial hearing loss. NISSHNL shows a better outcome than ISSNHL.

Project description:ImportancePatients with idiopathic sudden sensorineural hearing loss (ISSNHL) often experience permanent hearing impairment, which could result in psychological perturbations. However, the relationship between ISSNHL and affective disorders, including depression, anxiety, and bipolar disorder, has not been fully evaluated.ObjectiveTo investigate the potential relationship between ISSNHL and affective disorders using nationwide representative cohort sample data.Design, setting, and participantsThis study used a nationwide propensity score-matched cohort sample from the Korean National Health Insurance Service database from 2002 through 2013, which comprises data from approximately 1 million patients. The study included 1425 patients with ISSNHL and 7125 individuals without ISSNHL who were matched using propensity score matching, according to sociodemographic factors and enrollment year.Main outcomes and measuresSurvival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of developing affective disorders (anxiety, depression, and bipolar disorder) for each group.ResultsOf the total study population of 8550 (51.5% female), 961 developed affective disorders during the 11-year follow-up: 225 in the ISSNHL group (15.8%) and 736 in the comparison group (10.3%). We examined a total of 96 885.5 person-years (81 177.4 person-years in the comparison group and 15 708.1 person-years in the ISSNHL group). The incidence of affective disorders was 14.3 per 1000 person-years in the ISSNHL group and 9.1 per 1000 person-years in the comparison group. After adjustment for other factors, individuals with ISSNHL developed affective disorders more frequently than those in the comparison group (HR, 1.50; 95% CI, 1.30-1.75). Among the affective disorders, the HR of developing depression (HR, 1.66; 95% CI, 1.44-1.91) and anxiety disorder (HR, 1.79; 95% CI, 1.56-2.05) but not bipolar disorder (HR, 0.95; 95% CI, 0.54-1.70), was significantly greater in patients with ISSNHL.Conclusions and relevanceThis cohort study suggests that ISSNHL is associated with an increased incidence of affective disorders, specifically depression and anxiety. Therefore, these findings suggest that clinicians should monitor patients with ISSNHL carefully, and take specific precautions to reduce their risk of depression and anxiety disorder.

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RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss.

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RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss.

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