MicroRNA-34a targets sirtuin 1 and leads to diabetes-induced testicular apoptotic cell death

Jiao, Dan; Zhang, Huan; Jiang, Ziping; Huang, Wenlin; Liu, Zhuo; Wang, Zhaohui; Wang, Yonggang; Wu, Hao

doi:10.1007/s00109-018-1667-0

Cited by 19 publications

(14 citation statements)

References 63 publications

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“…Moreover, oxidative stress, neuronal apoptosis, ischemic infarction, and neurological deficits were dramatically decreased in MCAO rats when an miR-34a inhibitor was used. These data indicated that miR-34a was involved in oxidative stress and neuronal apoptosis, which is consistent with previous studies [11,35,36].…”

Section: Discussionsupporting

confidence: 93%

Inhibition of miR-34a ameliorates cerebral ischemia/reperfusion injury by targeting brain-derived neurotrophic factor

et al. 2021

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IntroductionOxidative stress and neuronal apoptosis are strongly associated with the pathogenesis of ischemic stroke. In this study, we aimed to determine whether miR-34a was involved in ischemia/reperfusion (I/R) injury, oxidative stress, and neuronal apoptosis by targeting brain-derived neurotrophic factor (BDNF).Material and methodsRats received middle cerebral artery occlusion (MCAO) surgery to simulate I/R injury. At 24 h after MCAO surgery, neurological deficits and infarct volumes were evaluated according to Longa’s scale and 2,3,5-triphenyltetrazolium (TTC) chloride staining. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and the expression of miR-34a and associated proteins were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting. Several markers of oxidative stress were detected using commercial kits, and the interaction between miR-34a and BDNF was measured by RNA immunoprecipitation (RIP).ResultsThe results showed that miR-34a was upregulated (p < 0.05), whereas BDNF was downregulated (p < 0.05) in the MCAO rats, and this negative correlation was accompanied by clear oxidative stress and neuronal apoptosis. RIP demonstrated a clear interaction between miR-34a and BDNF. Furthermore, miR-34a was also found to inhibit oxidative stress and neuronal apoptosis, increase BDNF expression, and ameliorate neurological deficits and infarct volumes (p < 0.05) seen in the MCAO rats.ConclusionsThese data suggested that inhibition of miR-34a ameliorated cerebral ischemia/reperfusion injury by targeting BDNF. This mechanism represents a novel and promising target for the treatment of strokes.

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Section: Discussionsupporting

confidence: 93%

Inhibition of miR-34a ameliorates cerebral ischemia/reperfusion injury by targeting brain-derived neurotrophic factor

et al. 2021

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“…In 2018, scientists found that hippocampal neural apoptosis may arise as a consequence of high blood glucose in the streptozotocin-induced diabetic mice in response to increased acetylation of p53 and downregulation of SIRT1 [44]. Another report indicated that miR-34a targeted SIRT1 mRNA, which induced apoptosis in the testicular tissue of diabetes-induced C57BL/6 male mice [45]. In accordance with these findings, we noticed that the expression of miR-34a in the pancreas of diabetic rats was associated with the concomitant up-regulation of SIRT1 and P53, and acceleration of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Swimming training attenuates pancreatic apoptosis through miR-34a/Sirtu in1/P53 Axis in high-fat diet and Streptozotocin-induced Type-2 diabetic rats

Alipour

Naderi

Alihemmati

et al. 2020

J Diabetes Metab Disord

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Objective The present study sought to evaluate the miR-34a/Sirtuin1/p53 pro-apoptotic pathway, and reveal its modulation in diabetic rats undergoing swimming exercise. Methods Twenty-eight male Wistar rats were divided into four groups. They were inducted to develop diabetes by injection of streptozotocin. After 12 weeks of swimming, the pancreatic tissue of these rats were removed to be evaluated for the expression level of Sitruin1/P53/miR-34a through qPCR. Results Findings indicated a marked rise in the expression of miR-34 and P53 (P < 0.01) as well as a significant decrease in expression of Sitruin1 (P < 0.01) in the diabetic group. In contrast, swimming resulted in a significant decrease in miR-34a expression (P < 0.01), and a prominent rise in the level of Sitruin1 in the swimming-trained-diabetic group (P < 0.01). Additionally, high, moderate and low apoptosis rate were observed in the pancreatic tissue of the diabetic, swimming-trained diabetic, and control groups, respectively. Conclusion Our findings suggested a correlation between pancreatic tissue apoptosis rate and miR-34a/Sitruin1/p53 signaling, that was subject to modulation by training.

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“…The induction of oxidative stress in the mouse testis results in an upregulation of miR-34a and downregulation of SIRT1. Upon oxidative stress, the testis displays higher expression of apoptotic markers and higher apoptotic index in male germ cells, indicating that oxidative stress is a major cause of male infertility ( 76 , 77 ). The members of the miR-34/449 family seems to exert significant anti-oxidant and anti-apoptotic properties and are vital for the testicular homeostatic mechanisms.…”

Section: The Role Of Mir-34/449 Family In Spermatogenesismentioning

confidence: 99%

Investigating the Role of the microRNA-34/449 Family in Male Infertility: A Critical Analysis and Review of the Literature

Pantos¹,

Grigoriadis

Tomara

et al. 2021

Front. Endocrinol.

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There is a great body of evidence suggesting that in both humans and animal models the microRNA-34/449 (miR-34/449) family plays a crucial role for normal testicular functionality as well as for successful spermatogenesis, regulating spermatozoa maturation and functionality. This review and critical analysis aims to summarize the potential mechanisms via which miR-34/449 dysregulation could lead to male infertility. Existing data indicate that miR-34/449 family members regulate ciliogenesis in the efferent ductules epithelium. Upon miR-34/449 dysregulation, ciliogenesis in the efferent ductules is significantly impaired, leading to sperm aggregation and agglutination as well as to defective reabsorption of the seminiferous tubular fluids. These events in turn cause obstruction of the efferent ductules and thus accumulation of the tubular fluids resulting to high hydrostatic pressure into the testis. High hydrostatic pressure progressively leads to testicular dysfunction as well as to spermatogenic failure and finally to male infertility, which could range from severe oligoasthenozoospermia to azoospermia. In addition, miR-34/449 family members act as significant regulators of spermatogenesis with an essential role in controlling expression patterns of several spermatogenesis-related proteins. It is demonstrated that these microRNAs are meiotic specific microRNAs as their expression is relatively higher at the initiation of meiotic divisions during spermatogenesis. Moreover, data indicate that these molecules are essential for proper formation as well as for proper function of spermatozoa per se. MicroRNA-34/449 family seems to exert significant anti-oxidant and anti-apoptotic properties and thus contribute to testicular homeostatic regulation. Considering the clinical significance of these microRNAs, data indicate that the altered expression of the miR-34/449 family members is strongly associated with several aspects of male infertility. Most importantly, miR-34/449 levels in spermatozoa, in testicular tissues as well as in seminal plasma seem to be directly associated with severity of male infertility, indicating that these microRNAs could serve as potential sensitive biomarkers for an accurate individualized differential diagnosis, as well as for the assessment of the severity of male factor infertility. In conclusion, dysregulation of miR-34/449 family detrimentally affects male reproductive potential, impairing both testicular functionality as well as spermatogenesis. Future studies are needed to verify these conclusions.

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MicroRNA-34a targets sirtuin 1 and leads to diabetes-induced testicular apoptotic cell death

Abstract: MiR-34a mediates diabetes-induced TACD via inhibition of SIRT1. The novel SIRT1 activator SRT2104 attenuates diabetes-induced TACD. MiR-34a inhibition activates SIRT1 and prevents diabetes-induced TACD.

Cited by 19 publications

References 63 publications

Inhibition of miR-34a ameliorates cerebral ischemia/reperfusion injury by targeting brain-derived neurotrophic factor

Inhibition of miR-34a ameliorates cerebral ischemia/reperfusion injury by targeting brain-derived neurotrophic factor

Swimming training attenuates pancreatic apoptosis through miR-34a/Sirtu in1/P53 Axis in high-fat diet and Streptozotocin-induced Type-2 diabetic rats

Investigating the Role of the microRNA-34/449 Family in Male Infertility: A Critical Analysis and Review of the Literature

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