CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis
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ABSTRACT:
PROVIDER: PRJNA645072 | ENA |
REPOSITORIES: ENA
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Project description:BackgroundBoth E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa.MethodsThe expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo.ResultsHere we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation.ConclusionsThese findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.
| S-EPMC7780414 | biostudies-literature
Project description:We overexpressed miR-212/132 by AAV9 in mouse model of doxorubicin-induced cardiotoxicity and wanted to identify myocardial targets of miR-212/132 in this model.
2018-12-29 | GSE121965 | GEO
Project description:Mice deficient for miR-212/132 have been reported to show impaired mammary gland development. However, another miR-212/132-deficient line does not demonstrate any obvious defects in mammary gland organogenesis. The transcriptome analysis in the mammary gland of the previously reported miR-212/132-deficient line by deep RNA-seq revealed significantly deregulated expression of genes flanking Mir-212/132 locus, such as HIC1, implying that the mammary gland phenotype might not be only due to loss of miR-212/132
2014-07-29 | GSE37952 | GEO
Project description:To study the differential expression of genes in prostate cancer tissue and benign prostatic hyperplasia
2022-09-01 | GSE154075 | GEO
Project description:To identify the target of miR-212, miR-132 and HIC1, we have employed whole genome microarray expression profiling on the human breast cancer MCF7 cells. To generate miR-212/132 or HIC1 inducible MCF7 cells, doxycycline-dependent miR-212/132 or HIC1 gene expression system was used. Either Tet-ON miR-212/132 MCF7 or Tet-ON HIC1 MCF7 were treated with 1μg/ml of Doxycycline for 36 hours with EMEM containing 0.01 mg/ml bovine insulin and 10% FCS. Two independent experiments were performed.
2014-07-29 | E-GEOD-37945 | biostudies-arrayexpress
Project description:miR-132 and miR-212 are structurally-related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same non-coding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/212 double knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/212 double knockout line explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/212 deletion increased the expression of 1,138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that, these two genes may function in a complex, non-redundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders
2016-03-01 | GSE73413 | GEO
Project description:Mice deficient for miR-212/132 have been reported to show impaired mammary gland development. However, another miR-212/132-deficient line does not demonstrate any obvious defects in mammary gland organogenesis. The transcriptome analysis in the mammary gland of the previously reported miR-212/132-deficient line by deep RNA-seq revealed significantly deregulated expression of genes flanking Mir-212/132 locus, such as HIC1, implying that the mammary gland phenotype might not be only due to loss of miR-212/132 Mammary gland mRNA profiles of Wild Type and Mir-212/132ILN/ILN mice were generated by deep sequencing using Illumina GAIIx.
2014-07-29 | E-GEOD-37952 | biostudies-arrayexpress
Project description:Transcriptomic profiling of miR-132/212-deficient and WT CD4 T cells isolated from spleens of L donovani infected mice (d28) to determine the effects of miR-132/212 on CD4 T cell activation in vivo. This was combined by transcriptomic analysis of early stage in vitro activated WT and miR-132/212-deficient CD4 T cells to identify direct miR-132/212 targets in CD4 T cells.
2019-03-22 | GSE125268 | GEO
Project description:To identify the target of miR-212, miR-132 and HIC1, we have employed whole genome microarray expression profiling on the human breast cancer MCF7 cells.
2014-07-29 | GSE37945 | GEO
Project description:To identify potential mechanisms underlying the phenotype of miR-132/212 KO mice under short photoperiods, we used quantitative mass spectrometry to analyze the SCN proteomes of miR-132/212 KO and WT mice under a 8:16 LD schedule at 4 time points, spaced 6h apart, across a 24h cycle (n=4 per time point per genotype). Quantification was achieved using a spike-in reference of three murine neural cell lines, including Neuro2A, and the adult mouse hypothalamic cell lines mHypoA-2/28 (CLU188) and mHypoA-SCN mix (CLU497) that had been labeled by SILAC (stable isotope labeling by amino acids in cell culture).
2017-04-24 | PXD003635 | Pride