miR-29b overexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC-1α signaling: Implications for age-related hearing loss

Xue, Tao; Li, Wei; Zha, Dingjun; Qiu, Jianhua; Chen, Fu Quan; Qiao, Li; Qiu, Yang

doi:10.3892/ijmm.2016.2735

Cited by 43 publications

(61 citation statements)

References 31 publications

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“…We further confirmed that miR-29b regulates SIRT1 by directly targeting its 3’UTR sequences, which adds a novel role for miR-29b as a ROS regulator in EOC development. Of note, our data are in agreement with previous reports demonstrating that miR-29s is capable of regulating SIRT1 in age-related hearing loss and self-renewal of mouse embryonic stem cells, adding a novel role of the tumor suppressor miRNA miR-29b in cancerous oxidative stress [24, 25]. Intriguingly, recent studies have observed a panel of differentially expressed miRNAs in urines of ovarian cancer patients as compared to healthy control [26].…”

Section: Discussionsupporting

confidence: 81%

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Hou

Zuo

et al. 2017

Cell Physiol Biochem

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Background: Metabolic abnormalities are frequently observed in multiple malignancies including epithelial ovarian cancer (EOC), among which imbalance between generation and elimination of reactive oxygen species (ROS) plays a critical role in EOC onset and progression. Here we investigated the role of miR-29b, a well-established tumor-suppressor miRNA in metabolic regulation of EOC cells. Methods: cell viability and apoptosis in miR-29b inhibited and over-expressed EOC cells were evaluated by CCK8 and Annexin V–FITC/PI assays. Change in miR-29b was detected in EOC cells incubated in H₂O₂ culture by q-PCR. Relative ROS levels were also detected in different EOC cultures, including modified miR-29b and SIRT1 levels as well as H₂O₂ incubation. A luciferase reporter assay was employed to detect the direct binding of miR-29b to SIRT1 3’ UTR. Changes in cell viability and ROS levels were assessed in SIRT1-knocked down EOC cells. Results: miR-29b expression correlates with decreased EOC cell viability and increased apoptosis. H₂O₂ downregulated miR-29b in a time and dose-dependent manner. miR-29b expression negatively correlated with ROS levels, whereas SIRT1 significantly stimulated ROS formation. Luciferase reporter assays confirmed miR-29b downregulation of SIRT1by directly targeting its mRNA 3’-UTR. SIRT1 silencing rescues cell viability of H₂O₂ treated cells. Also, SIRT1 inhibition blocked cell apoptosis induced by H₂O₂ as well as reduced intracellular ROS levels. Conclusion: Together, our findings indicated that the miR-29b/SIRT1 axis has a protective effect against H₂O₂-induced damage of cell viability and oxidative stress and may provide novel options for miR-29b-based therapeutic approaches for EOC treatment.

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Section: Discussionsupporting

confidence: 81%

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Hou

Zuo

et al. 2017

Cell Physiol Biochem

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“…We are in the process of exploring the viability of using different techniques based on microRNAs specific for hair cells and SGs [12,13] for monitoring hearing loss progression. Due to their high sensitivity to detect cells death [9] and altered function [8], microRNAs may provide a valid alternative to traditional ABR test.…”

Section: Editorialmentioning

confidence: 99%

“…In MELAS, mitochondria that have been damaged (by deletion/mutation in their DNA) increase the Redox Oxidative Species (ROS) concentration [8] and cell apoptosis [9] which reduce the number of inner ear cells (SG, VS and Hair cells) and, cause a malfunction of the remaining cells.…”

mentioning

confidence: 99%

Auditory Brainstem Response and Hearing Loss in MELAS: Post Mortem Analysis of Temporal Bone to Explain Abnormal ABR

Arianna¹,

Antonietta²,

Dipietro³

et al. 2018

JOENTR

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We observed a MELAS patient who came to our Clinical Center for moderate SNHL. The ABR from this patient displayed waves (Figure 1) with amplitude and latency too reduced to be considered within the normal range, but not completely absent as it would be expected considering his auditory threshold in pure tone audiometry (PTA).In an attempt to explain this observation, we reviewed the literature on the temporal bone aspect of MELAS patients. Loss of Spiral Ganglions (SGs) and atrophy of Stria Vascularis (SV) are typical findings in temporal bone of patients with MELAS even when the Organ of Corti is entirely preserved.In SGs and SV mitochondria are abundant [7], as they are necessary to support the high metabolic functions of these structures. In MELAS, mitochondria that have been damaged (by deletion/mutation in their DNA) increase the Redox Oxidative Species (ROS) concentration [8] and cell apoptosis [9] which reduce the number of inner ear cells (SG, VS and Hair cells) and, cause a malfunction of the remaining cells.ABR reflects the way the auditory signal travels from the retrocochlear portion (synapse, SGs, cochlear nerve and cochlear nuclei) (Waves I, III) to the cortex (wave V); if all the structures in the retro-cochlear hearing pathways function correctly, the ABR displays normal amplitude and latency; but damage in even one of the structures causes abnormal ABR latency and/or amplitude, which in turn alter the overall signal shape.We think that the abnormal ABR of our patient can be explained by the altered functions of residual SGs, which cannot sufficiently amplify the signal to generate an actual ABR wave. The numerous mitochondrial mutations observed in the temporal bone of patients with MELAS [10][11] support the idea that the residual SGs do not function well enough to allow a correct transmission of the impulse, which in turn leads to an abnormal ABR. Arguably, the high ABR variability in MELAS patients reported in the literature [2,3,4,6] is due to the stochastic segregation of mitochondria during embryogenesis; the concentration of damaged mitochondria could differ among patients just due to

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“…In studies involving aging and the apoptotic loss of cochlear hair cells, high expression of miR-29b in aged C57BL/6 mice results in decreased expression of SIRT1 and mitochondrial dysfunction, suggesting a protective role for SIRT1 (147). Diabetic endothelial vascular dysfunction that occurs during hyperglycemia elevated free fatty acids can result from the up-regulation of miR-34a that depresses the expression of SIRT1.…”

Section: Sirt1 Mirnas and Vascular Diseasementioning

confidence: 99%

Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

Maiese¹

2017

CNR

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Noncommunicable diseases (NCDs) contribute to a significant amount of disability and death in the world. Of these disorders, vascular disease is ranked high, falls within the five leading causes of death, and impacts multiple other disease entities such as those of the cardiac system, nervous system, and metabolic disease. Targeting the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) pathway and the modulation of micro ribonucleic acids (miRNAs) may hold great promise for the development of novel strategies for the treatment of vascular disease since each of these pathways are highly relevant to cardiac and nervous system disorders as well as to metabolic dysfunction. SIRT1 is vital in determining the course of stem cell development and the survival, metabolism, and life span of differentiated cells that are overseen by both autophagy and apoptosis. SIRT1 interfaces with a number of pathways that involve forkhead transcription factors, mechanistic of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Wnt1 inducible signaling pathway protein 1 (WISP1) such that the level of activity of SIRT1 can become a critical determinant for biological and clinical outcomes. The essential fine control of SIRT1 is directly tied to the world of non-coding RNAs that ultimately oversee SIRT1 activity to either extend or end cellular survival. Future studies that can further elucidate the crosstalk between SIRT1 and non-coding RNAs should serve well our ability to harness the power of SIRT1 and non-coding RNAs for the treatment of vascular disorders.

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miR-29b overexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC-1α signaling: Implications for age-related hearing loss

Cited by 43 publications

References 31 publications

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Auditory Brainstem Response and Hearing Loss in MELAS: Post Mortem Analysis of Temporal Bone to Explain Abnormal ABR

Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

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