MicroRNA-34a promoting apoptosis of human lens epithelial cells through down-regulation of B-cell lymphoma-2 and silent information regulator

Li, Qinglan; Zhang, Hongyang; Qin, Y.; Meng, Qianli; Xl, Yao; Guo, Huiling

doi:10.18240/ijo.2016.11.04

Cited by 15 publications

(10 citation statements)

References 22 publications

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“…CircRNAs can also serve as ceRNAs to prevent miRNAs from silencing their target genes [ 19 , 25 ]. Many miRNAs, such as miR-34a-5p, miR-15a, and miR-23b-3p, have been reported to be significantly up-regulated in ARC lens tissues compared to normal tissues and exert important effects on cataract formation [ 47 – 51 ]. Based on the interaction between circRNAs and miRNAs, we identified candidate circRNAs which were down-regulated in ARC and interacted with miRNAs involved in oxidative stress and apoptosis for subsequent studies.…”

Section: Resultsmentioning

confidence: 99%

“…MiRNAs, a group of small non-coding regulatory RNAs of 21-23 nucleotides in length, can regulate gene expression through base-pairing with 3' untranslated regions (3’UTR) of their target mRNAs [ 57 ]. Involved in the intracellular processes of cataracts, including apoptosis, proliferation, activity, and oxidative damage [ 50 ], several miRNAs, like miR-34a-5p [ 47 , 48 ], miR-15a [ 49 ], miR-23b-3p [ 51 ], and miR-211-5p [ 58 , 59 ], could be specifically up-expressed in the lens and regulate the apoptosis or oxidative stress of LECs in the formation of ARC in experimental studies. Naturally, we selected circRNAs which were capable of binding these miRNAs based on databases (TargetScan, miRanda, and StarBase).…”

Section: Discussionmentioning

confidence: 99%

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Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p

Liang

Dou

et al. 2020

Aging

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Age-related cataract (ARC) is one of the major causes of visual impairment and reversible blindness worldwide. Accumulating evidence has revealed that circular RNAs (circRNAs) are involved in multiple regulatory processes in various ocular diseases. However, the expression profile, regulatory roles, and underlying mechanisms of circRNAs in ARC remain largely unknown. Herein we deep-sequenced circRNAs of anterior lens capsules from normal and ARC lenses, and detected 23,787 candidate circRNAs. Of these, 466 were significantly differentially expressed, and a higher correlation in down-regulated circRNAs between ARC and diabetic cataract was observed compared with up-regulated ones. Subsequent bioinformatics analysis disclosed that certain differentially expressed circRNAs participated in oxidative stress and apoptosis-related signaling pathways in ARC. Notably, the level of circZNF292 was significantly decreased, while miR-23b-3p was significantly increased in ARC. The target region prediction and dual-luciferase reporter assays proved that circZNF292 acted as a competitive endogenous RNA to regulate the expression of anti-oxidative genes through competing with miR-23b-3p. Our results indicate that circZNF292, a down-regulated circRNA in the anterior lens capsule of ARC patients, may be involved in resistance to oxidative damage and apoptosis of lens epithelial cells by sponging miR-23b-3p, providing a potential target for prevention and treatment of ARC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p

Liang

Dou

et al. 2020

Aging

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“…MiR-34a was highly expressed in unclear, cortical and posterior subcapsular cataract tissues and was correlated with lens opacity severity [ 33 ]. Moreover, miR-34a could enhance the apoptosis by downregulating Bcl-2 and SIRT1 in human LECs [ 34 ]. Let-7b is correlated with age-related cataract and can enhance the ultraviolet irradiation-induced apoptosis of LECs [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-30a inhibits BECN1-mediated autophagy in diabetic cataract

2017

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PurposeTo investigate the role of microRNAs in the regulation of autophagy and apoptosis in lens epithelial cells (LECs) during diabetic cataract formation.MethodsA miRNA microarray study and quantitative real-time PCR were performed to identify the expression of miRNAs in LECs of diabetic cataract. Human LECs were cultured in high glucose conditions as a diabetic cataract model. BECN1 and LC3B were detected by Western blotting and quantitative real-time PCR. The extent of apoptosis was measured using FACSCalibur flow cytometry.ResultsDownregulation of miR-30a was identified in LECs attached to diabetic cataract tissues. By the bioinformatic assay and the luciferase activity assay, BECN1 was found to be a direct target of miR-30a. MiR-30a reduced the BECN1-mediated autophagy activity induced by high glucose in LECs in vitro. The ratio of LECs apoptosis was also decreased.ConclusionMiR-30a was involved in the inhibition of autophagy by targeting BECN1 in LECs in human diabetic cataract.

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“…Recently, regulating RNAs that control gene expression has raised increasing attention in various situations. Although the role of microRNAs (miRNAs) in lenses is well established, 26 , 27 the role of lncRNAs in lens development and cataracts is still poorly understood. With previous studies reporting the existence of lncRNAs in lens development, 18 , 19 , 20 novel lncRNA ALB is the first, to our knowledge, to potentially play a role in human lens development.…”

Section: Discussionmentioning

confidence: 99%

A New Long Noncoding RNA ALB Regulates Autophagy by Enhancing the Transformation of LC3BI to LC3BII during Human Lens Development

Qin

Zhang

et al. 2017

Molecular Therapy - Nucleic Acids

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Autophagy is essential in lens organelle degradation. This study aimed to seek potential autophagy-associated long noncoding RNAs (lncRNAs) and their relative mechanisms in human lens development using the “fried egg” lentoid body (LB) generation system. The expression pattern of LC3B in differentiating LBs was similar to that in developing a mouse lens in vivo. Among the massive lncRNAs expressed with a significant difference between induced pluripotent stem cells (iPSCs) and LBs, lncRNA affecting LC3B (ALB), which was predicted to have a co-relationship with the autophagy marker LC3B, was highly expressed in differentiating lens fibers in LBs. This result was consistent with its high expression in human embryonic lenses compared to those in embryonic stem cells (ESCs). Furthermore, lncRNA ALB knockdown resulted in the downregulation of LC3BII at the protein level, therefore inhibiting the autophagy process in human lens epithelial cells (HLECs). Our results identify lncRNA ALB, a potential autophagy regulator in organelle degradation during human lens development, highlighting the importance of lncRNAs in lens development.

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MicroRNA-34a promoting apoptosis of human lens epithelial cells through down-regulation of B-cell lymphoma-2 and silent information regulator

Abstract: MiR-34a promotes the apoptosis of HLE-B3 cells by down-regulating Bcl-2 and SIRT1, suggesting that miR-34a may involve in the pathogenesis of cataract formation and targeting miR-34a may be a potentially therapeutic approach for treatment of cataract.

Cited by 15 publications

References 22 publications

Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p

Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p

MiR-30a inhibits BECN1-mediated autophagy in diabetic cataract

A New Long Noncoding RNA ALB Regulates Autophagy by Enhancing the Transformation of LC3BI to LC3BII during Human Lens Development

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