MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6

Xu, Shun; Huang, Huawen; Li, Nanhong; Zhang, Bing; Jia, Ya; Yang, Yu-Kun; Yuan, Yuan; Xiong, Xing‐Dong; Wang, Dengchuan; Zheng, Heng; Liu, Xinguang

doi:10.1016/j.bbrc.2016.04.016

Cited by 9 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The primary mouse embryonic fibroblasts (MEFs) were prepared from C57BL/6 mouse as our previously described (Xu et al, ), then the prepared cells were frozen in aliquots as passage 0 (P0). NIH/3T3, an immortalised mouse embryonic fibroblasts, and HK293T, a SV40‐transformed human embryonic kidney cell line.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

Zhang

Zhu

et al. 2017

Cell Biology International

Self Cite

View full text Add to dashboard Cite

MicroRNA-194 (miR-194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti-proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR-194's contribution to cellular senescence is limited. We herein sought to explore the role of miR-194 in the replicative senescence and stress-induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR-194 is highly expressed in senescent cells, and extra expression of miR-194 significantly triggers the replicative senescence of MEFs and H O -induced senescence of NIH/3T3 cells, while inhibition of miR-194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR-194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR-194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Cell proliferation was evaluated by measuring DNA synthesis with the BrdU cell proliferation assay (Sigma, USA) as we previously described (Xu et al, ).…”

Section: Methodsmentioning

confidence: 99%

miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

Zhang

Zhu

et al. 2017

Cell Biology International

Self Cite

View full text Add to dashboard Cite

show abstract

“…The downregulation of CDK6 was necessary to demonstrate remarkably deteriorating cardiovascular disease risk by destroying the vascular endothelial structure and function [ 19 ]. Moreover, the replicating biological process of fibroblasts in mouse embryo was intensified possibly by containing CDK6 expression [ 20 ]. In our study, the expression of CDK6 decreased significantly likely because of the enrichment of the PI3K/AKT pathway at an early stage of MI.…”

Section: Discussionmentioning

confidence: 99%

Identification of Genetic Biomarkers for Diagnosis of Myocardial Infarction Compared with Angina Patients

Zhang

Tian

Liu

et al. 2020

Cardiovascular Therapeutics

View full text Add to dashboard Cite

Background. Myocardial infarction (MI) is the most terrible appearance of cardiovascular disease. The incidence of heart failure, one of the complications of MI, has increased in the past few decades. Therefore, the identification of MI from angina patients and the determination of new diagnoses and therapies of MI are increasingly important. The present study was aimed at identifying differentially expressed genes and miRNAs as biomarkers for the clinical and prognosis factors of MI compared with angina using microarray data analysis. Methods. Differentially expressed miRNAs and genes were manifested by GEO2R. The biological function of differentially expressed genes (DEGs) was examined by GO and KEGG. The construction of a protein-protein network was explored by STRING. cytoHubba was utilized to screen hub genes. Analysis of miRNA-gene pairs was executed by the miRWalk 3.0 database. The miRNA-target pairs overlapped with hub genes were seen as key genes. Logistic regressive analysis was performed by SPSS. Results. A number of 779 DEGs were recorded. The biological function containing extracellular components, signaling pathways, and cell adhesion was enriched. Twenty-four hub genes and three differentially expressed miRNAs were noted. Eight key genes were demonstrated, and 6 out of these 8 key genes were significantly related to clinical and prognosis factors following MI. Conclusions. CALCA, CDK6, MDM2, NRXN1, SOCS3, VEGFA, SMAD4, NCAM1, and hsa-miR-127-5p were thought to be potential diagnosis biomarkers for MI. Meanwhile, CALCA, CDK6, NRXN1, SMAD4, SOCS3, and NCAM1 were further identified to be potential diagnosis and therapy targets for MI.

show abstract

“…C57BL/6 mice of male were sacrificed at 20 months (Aging) or 2 months (Young) old in the experiments; then, the kidney, lung, liver, heart, and brain tissues were obtained from both groups. The primary MEF cells were prepared from C57BL/6 mouse have been previously described (Xu et al, ) and considered as passage 0 (designated as P0). HK293T was a SV40‐transformed embryonic kidney cell line, and NIH/3T3 was an immortalized mouse embryonic fibroblasts.…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was determined by the Alamar Blue assay (AbD Serotec, UK) as previously described (Xu et al, ). Briefly, MEFs were firstly seeded in a 96‐well plate at 50% confluence; 24 hr later, the cells were transfected with RNA oligoribonucleotide(s) and followed by the Alamar Blue assay at indicated times.…”

Section: Methodsmentioning

confidence: 99%

The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway

Huang

et al. 2019

Aging Cell

Self Cite

View full text Add to dashboard Cite

Aging is a multifactorial process characterized by the progressive deterioration of physiological functions. Among the multiple molecular mechanisms, microRNAs (miRNAs) have increasingly been implicated in the regulation of Aging process. However, the contribution of miRNAs to physiological Aging and the underlying mechanisms remain elusive. We herein performed high‐throughput analysis using miRNA and mRNA microarray in the physiological Aging mouse, attempted to deepen into the understanding of the effects of miRNAs on Aging process at the “network” level. The data showed that various p53 responsive miRNAs, including miR‐124, miR‐34a and miR‐29a/b/c, were up‐regulated in Aging mouse compared with that in Young mouse. Further investigation unraveled that similar as miR‐34a and miR‐29, miR‐124 significantly promoted cellular senescence. As expected, mRNA microarray and gene co‐expression network analysis unveiled that the most down‐regulated mRNAs were enriched in the regulatory pathways of cell proliferation. Fascinatingly, among these down‐regulated mRNAs, Ccna2 stood out as a common target of several p53 responsive miRNAs (miR‐124 and miR‐29), which functioned as the antagonist of p21 in cell cycle regulation. Silencing of Ccna2 remarkably triggered the cellular senescence, while Ccna2 overexpression delayed cellular senescence and significantly reversed the senescence‐induction effect of miR‐124 and miR‐29. Moreover, these p53 responsive miRNAs were significantly up‐regulated during the senescence process of p21‐deficient cells; overexpression of p53 responsive miRNAs or knockdown of Ccna2 evidently accelerated the cellular senescence in the absence of p21. Taken together, our data suggested that the p53/miRNAs/Ccna2 pathway might serve as a novel senescence modulator independent of p53/p21 pathway.

show abstract

MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6

Cited by 9 publications

References 33 publications

miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

Identification of Genetic Biomarkers for Diagnosis of Myocardial Infarction Compared with Angina Patients

The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway

Contact Info

Product

Resources

About