MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh/Hdh cells

Das, Eashita; Jana, Nihar Ranjan; Bhattacharyya, Nitai P.

doi:10.1016/j.bbrc.2013.06.041

Cited by 39 publications

(24 citation statements)

References 36 publications

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“…Expectedly, our data uncovered Ccna2 were evidently down‐regulated in the Aging mouse tissues and senescent MEF cells, similar as multiple other cell cycle regulators, and silencing of Ccna2 significantly enhanced the premature senescence phenotype, which established a direct relationship between Ccna2 and cellular senescence. Our results further showed that Ccna2 was the common target of several Aging‐related miRNAs, including miR‐124 and miR‐29, which was consistent with the previous evidence that miR‐124 direct target Ccna2 (Das, Jana, & Bhattacharyya, ). What's more, the miRNA–target prediction analysis revealed that Ccna2 3'UTR contains candidate binding site with more other p53 responsive miRNAs (such as miR‐199a and miR‐194), indicating of the pivotal role of Ccna2 in the Aging‐related p53/miRNAs/Ccna2 pathway.…”

Section: Discussionsupporting

confidence: 92%

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

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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.

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Section: Discussionsupporting

confidence: 92%

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

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“…However, the genes specifically controlling the size of DP and matrix remain elusive. In the present study, the up-regulated genes in the super fine wool group included 5 genes associated with the cell cycle and apoptosis: GSDMA3 [56], HSPA2 [57], RPS27A [58], PDCD6IP [59], DAP [60], CCNA2 [61] and FOS [62]; the down-regulated genes included 7 genes associated with promoting follicle cell proliferation and differentiation: KRT1 [63, 64], KRT7 [65, 66], HSD11B1 [67, 68], S100A8 [41, 69, 70], NT5C3 L [71] and DNAJC12 [72]. These genes may through promoting HF cell apoptosis, inhibiting follicle cell proliferation and differentiation, thereby reduce the WFD.…”

Section: Discussionmentioning

confidence: 99%

Exploring Differentially Expressed Genes and Natural Antisense Transcripts in Sheep (Ovis aries) Skin with Different Wool Fiber Diameters by Digital Gene Expression Profiling

et al. 2015

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Wool fiber diameter (WFD) is the most important economic trait of wool. However, the genes specifically controlling WFD remain elusive. In this study, the expression profiles of skin from two groups of Gansu Alpine merino sheep with different WFD (a super-fine wool group [FD = 18.0 ± 0.5 μm, n= 3] and a fine wool group [FD=23.0±0.5μm, n=3]) were analyzed using next-generation sequencing–based digital gene expression profiling. A total of 40 significant differentially expressed genes (DEGs) were detected, including 9 up-regulated genes and 31 down-regulated genes. Further expression profile analysis of natural antisense transcripts (NATs) showed that more than 30% of the genes presented in sheep skin expression profiles had NATs. A total of 7 NATs with significant differential expression were detected, and all were down-regulated. Among of 40 DEGs, 3 DEGs (AQP8, Bos d2, and SPRR) had significant NATs which were all significantly down-regulated in the super-fine wool group. In total of DEGs and NATs were summarized as 3 main GO categories and 38 subcategories. Among the molecular functions, cellular components and biological processes categories, binding, cell part and metabolic process were the most dominant subcategories, respectively. However, no significant enrichment of GO terms was found (corrected P-value >0.05). The pathways that were significantly enriched with significant DEGs and NATs were mainly the lipoic acid metabolism, bile secretion, salivary secretion and ribosome and phenylalanine metabolism pathways (P < 0.05). The results indicated that expression of NATs and gene transcripts were correlated, suggesting a role in gene regulation. The discovery of these DEGs and NATs could facilitate enhanced selection for super-fine wool sheep through gene-assisted selection or targeted gene manipulation in the future.

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“…BTG1 exerts cellular functions by interacting with PRMT1, HOXB9, and hCAF1, which regulate the expression of a number of genes involved in cell cycle control and progression [ 41 – 43 ]. CCNA2 (cyclinA2) physically associates with BTG1 [ 44 ] and controls S phase by activating CDK2 kinases to initiate DNA synthesis [ 45 ]. Ectopic over-expression of CCNA2 triggers checkpoint response and subsequently increases the S phase population in mammalian cells [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells

Ding

et al. 2014

Radiat Oncol

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BackgroundB cell translocation gene 1 (BTG1) has long been recognized as a tumor suppressor gene. Recent reports demonstrated that BTG1 plays an important role in progression of cell cycle and is involved in cellular response to stressors. However, the microRNAs mediated regulatory mechanism of BTG1 expression has not been reported so far. MicroRNAs can effectively influence tumor radiosensitivity by preventing cell cycle progression, resulting in enhancement of the cytotoxicity of radiotherapy efficacy. This study aimed to demonstrating the effects of microRNAs on the BTG1 expression and cellular radiosensitivity.MethodsThe human renal carcinoma 786-O cells were treated with 5 Gy of X-rays. Expressions of BTG1 gene and miR-454-3p, which was predicted to target BTG1 by software algorithm, were analyzed by quantitative polymerase chain reaction. Protein expressions were assessed by Western blot. Luciferase assays were used to quantify the interaction between BTG1 3′-untranslated region (3′-UTR) and miR-454-3p. The radiosensitivity was quantified by the assay of cell viability, colony formation and caspase-3 activity.ResultsThe expression of the BTG1 gene in 786-O cells was significantly elevated after treatments with X-ray irradiation, DMSO, or serum starvation. The up-regulation of BTG1 after irradiation reduced cellular radiosensitivity as demonstrated by the enhanced cell viability and colony formation, as well as the repressed caspase-3 activity. In comparison, knock down of BTG1 by siRNA led to significantly enhanced cellular radiosensitivity. It was found that miR-454-3p can regulate the expression of BTG1 through a direct interaction with the 3′-UTR of BTG1 mRNA. Decreasing of its expression level correlates well with BTG1 up-regulation during X-ray irradiation. Particularly, we observed that over-expression of miR-454-3p by transfection inhibited the BTG1 expression and enhanced the radiosensitivity. In addition, cell cycle analysis showed that over-expression of miR-454-3p shifted the cell cycle arrest from G2/M phase to S phase.ConclusionsOur results indicate that BTG1 is a direct target of miR-454-3p. Down-regulation of BTG1 by miR-454-3p renders tumor cells sensitive to radiation. These results may shed light on the potential application in tumor radiotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/1748-717X-9-179) contains supplementary material, which is available to authorized users.

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MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh/Hdh cells

Cited by 39 publications

References 36 publications

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

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

Exploring Differentially Expressed Genes and Natural Antisense Transcripts in Sheep (Ovis aries) Skin with Different Wool Fiber Diameters by Digital Gene Expression Profiling

Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells

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