MicroRNA-125b inhibits lens epithelial cell apoptosis by targeting p53 in age-related cataract

Yu, Qin; Zhao, Jing; Min, Xiaojie; Wang, Mingwu; Luo, Wenting; Wu, Di; Yan, Qichang; Li, Jing; Wu, Xinwei; Zhang, Jinsong

doi:10.1016/j.bbadis.2014.10.002

Cited by 57 publications

(30 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TP53, the second candidate to link miRNA precursor transfection to MX1, has previously been validated as a target of miRNA-125b by several studies (37)(38)(39). As expected, transfection of miR-125b precursor alone or the miRNA precursor pool reduced TP53 expression in THP-1 cells (Fig.…”

Section: Resultssupporting

confidence: 56%

“…It is possible that the direct inhibition of RIG-I by miR-221, as well as the inhibited activation of MX1 by RIG-I, is contributing to the replication effect observed in this study. TP53, the other established miRNA-responsive controller of MX1, is a direct target of miR-125b (37)(38)(39) and is a master regulator of the cellular mechanisms controlling responses to cellular stress such as DNA damage, aberrant oncogene activation, loss of normal cell-cell contacts, nutrient deprivation, and abnormal reactive oxygen species production. Importantly, it is also induced in response to viral infection as a downstream transcriptional target of type I IFN signaling (82).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1

Herkt

Caffrey

Surmann

et al. 2020

mBio

View full text Add to dashboard Cite

Legionella pneumophila is an important cause of pneumonia. It invades alveolar macrophages and manipulates the immune response by interfering with signaling pathways and gene transcription to support its own replication. MicroRNAs (miRNAs) are critical posttranscriptional regulators of gene expression and are involved in defense against bacterial infections. Several pathogens have been shown to exploit the host miRNA machinery to their advantage. We therefore hypothesize that macrophage miRNAs exert positive or negative control over Legionella intracellular replication. We found significant regulation of 85 miRNAs in human macrophages upon L. pneumophila infection. Chromatin immunoprecipitation and sequencing revealed concordant changes of histone acetylation at the putative promoters. Interestingly, a trio of miRNAs (miR-125b, miR-221, and miR-579) was found to significantly affect intracellular L. pneumophila replication in a cooperative manner. Using proteome-analysis, we pinpointed this effect to a concerted downregulation of galectin-8 (LGALS8), DExD/H-box helicase 58 (DDX58), tumor protein P53 (TP53), and then MX dynamin-like GTPase 1 (MX1) by the three miRNAs. In summary, our results demonstrate a new miRNA-controlled immune network restricting Legionella replication in human macrophages. IMPORTANCE Cases of Legionella pneumophila pneumonia occur worldwide, with potentially fatal outcome. When causing human disease, Legionella injects a plethora of virulence factors to reprogram macrophages to circumvent immune defense and create a replication niche. By analyzing Legionella-induced changes in miRNA expression and genomewide chromatin modifications in primary human macrophages, we identified a cell-autonomous immune network restricting Legionella growth. This network comprises three miRNAs governing expression of the cytosolic RNA receptor DDX58/RIG-I, the tumor suppressor TP53, the antibacterial effector LGALS8, and MX1, which has been described as an antiviral factor. Our findings for the first time link TP53, LGALS8, DDX58, and MX1 in one miRNA-regulated network and integrate them into a functional node in the defense against L. pneumophila.

show abstract

Section: Resultssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1

Herkt

Caffrey

Surmann

et al. 2020

mBio

View full text Add to dashboard Cite

show abstract

“…Besides Smad4, many other target genes of miR-125b-5p and their sophisticated functions have been intensively studied by many previous studies. In lens epithelial cell, miR-125b was confirmed to directly target p53 [42] which plays important roles in cell apoptosis. In glioblastoma stem cells, miR-125b-5p is capable of regulating the E2F2 expression and affects cellular proliferation [43].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-125b-5p inhibits proliferation and promotes adipogenic differentiation in 3T3-L1 preadipocytes

Ouyang

Guo

et al. 2015

ABBS

View full text Add to dashboard Cite

Previous evidence has indicated that the microRNA-125b (miR-125b) family plays important roles in the regulation of cancer cell growth, development, differentiation, and apoptosis. However, whether they contribute to the process of adipocyte differentiation remains unclear. In the present study, we revealed that the expression level of miR-125b-5p, a member of miR-125b family, was dramatically up-regulated during differentiation of 3T3-L1 preadipocyte into mature adipocyte. Supplement of miR-125b-5p into 3T3-L1 cells promoted adipogenic differentiation as evidenced by increased lipid droplets and mRNA levels of adipocyte-specific molecular markers, including peroxisome proliferators-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid-binding protein 4, and lipoprotein lipase, and by triglyceride accumulation. CCK-8 assay showed that miR-125b-5p supplementation significantly inhibited cell proliferation. Flow cytometry analysis showed that miR-125b-5p impaired G1/S phase transition as well as the mRNA and protein expression of G1/S-related genes, such as Cyclin D2, Cyclin D3, and CDK4. Nevertheless, it had no effect on apoptosis. Additionally, by target gene prediction, we demonstrated that smad4 may be a potential target of miR-125b-5p in mouse 3T3-L1 preadipocytes, accounting for some of miR-125b-5p's functions. Taken together, these data indicated that miR-125b-5p may serve as an important positive regulator in adipocyte differentiation, at least partially through down-regulating smad4.

show abstract

“…The presence of epithelial-mesenchymal transition (EMT) during epithelial cell differentiation into fiber cells has been reported in the progress of cataract formation 8–13 . MicroRNAs (miRNAs) are a group of noncoding small RNAs and have been found to be associated with cell differentiation, proliferation, and apoptosis 14–16 . We previously detected that miR-204-5p could directly regulate EMT by targeting SMAD4 in posterior capsule opacification (PCO) known as a complication of cataract surgery 17 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-30a Regulation of Epithelial-Mesenchymal Transition in Diabetic Cataracts Through Targeting SNAI1

Zhang

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process in development, fibrosis, and metastasis. During the process, epithelial cells lose their morphology and transcriptional program, and transdifferentiate to mesenchymal cells. It has been reported that lens epithelial cells undergo EMT during cataract formation, and regulation of microRNAs on genes is associated with lens development. However, the molecular mechanisms of this regulation in diabetic cataract still need to be investigated. In the present study, the expression of E-cadherin was downregulated, while the expression of alpha-SMA and vimentin was upregulated in diabetic cataract tissues and the in vitro model, suggesting the involvement of EMT in diabetic cataract formation. Results of miRNA profiling demonstrated that miR-30a was markedly downregulated in diabetic cataract tissues. Overexpression of miR-30a-5p decreased SNAI1, a known modulator of EMT, and the expression of vimentin and alpha-SMA in our diabetic cataract model in vitro. It is concluded that EMT is involved in human diabetic cataract, and upregulation of miR-30a can repress EMT through its targeting of SNAI1 in lens epithelial cells, which make miR-30a a novel target of therapeutic intervention for human diabetic cataract.

show abstract

MicroRNA-125b inhibits lens epithelial cell apoptosis by targeting p53 in age-related cataract

Cited by 57 publications

References 39 publications

A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1

A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1

MicroRNA-125b-5p inhibits proliferation and promotes adipogenic differentiation in 3T3-L1 preadipocytes

MicroRNA-30a Regulation of Epithelial-Mesenchymal Transition in Diabetic Cataracts Through Targeting SNAI1

Contact Info

Product

Resources

About