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MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression.

ABSTRACT: microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE14831 | GEO | 2009/02/19

SECONDARY ACCESSION(S): PRJNA112071

REPOSITORIES: GEO

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MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression.

Project description:microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions. HCT116 Dicerex5 cells were transfected with microRNAs in six-well plates, and RNA was isolated 10 h after transfection. Transcripts containing the miR-106b family hexamers in their 3' UTRs were identified. By microarray analysis, 103 transcripts that contained miR-106b family complementary hexamers in their 3' UTRs were down-regulated by miR-106b, miR-106a, miR-20b, and miR-17-5p within 10 h of transfection.

2010-06-23 | E-GEOD-14831 | biostudies-arrayexpress

miR-17-92/106b regulate beta cell mitotic checkpoint and insulin secretion

Project description:Adult beta cells in the pancreas are the sole source of insulin in our body. Beta cell loss or increased demand for insulin, impose metabolic challenges because adult beta cells are generally quiescent and infrequently re-enter the cell division cycle. miR-17-92/106b is a family of proto-oncogene microRNAs, that regulate proliferation in normal tissues and in cancer. Here, we employ mouse genetics to demonstrate a critical role for miR-17-92/106b in glucose homeostasis and in controlling insulin secretion. Mass spectrometry analysis was performed on miR-17-92LoxP/LoxP;106-25-/- MEF lysate, without or with CRE-Adenovirus. miR-17-92LoxP/LoxP;106-25+/+ MEFs with GFP-Adenovirus served as controls. We demonstrate that miR-17-92/106b regulate the adult beta cell mitotic checkpoint and that miR-17-92/106b deficiency results in reduction in beta cell mass in-vivo. Furthermore, protein kinase A (PKA) is a new relevant molecular pathway downstream of miR-17-92/106b in control of adult beta cell division and glucose homeostasis. Therefore, contributes to the understanding of proto-oncogene miRNAs in the normal, untransformed endocrine pancreas, and illustrates new genetic means for regulation of beta cell mitosis and function by non-coding RNAs.

2019-06-17 | PXD012610 | Pride

Homo sapiens

Project description:MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression.

| PRJNA112071 | ENA

MiR-106b-25 cluster targets caspase 7 and focal adhesion in human prostate cancer

Project description:We and others previously reported that the miR-106b-25 microRNA cluster is a candidate oncogene in human prostate cancer. Here, we made the novel observation that miR-106b-25 expression is further up-regulated in distant metastasis. Moreover, increased tumor miR-106b expression was associated with early disease recurrence. To identify yet unknown oncogenic functions of the prognostic miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that caspase-7 is a candidate direct target of miR-106b, which was confirmed by Western blot analysis and a 3’UTR reporter assay. Other analyses showed that caspase-7 is down-regulated in primary human prostate tumors and metastatic lesions across multiple datasets and is by itself associated with disease recurrence. Using bioinformatics, we also discovered that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally confirmed using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and metastasis and may do so by altering apoptosis- and focal adhesion-related pathways. To elucidate the effects miR-106b, we up-regulated miR-106b in LNCaP cells and examined gene expression alterations on a global scale with Affymetrix arrays.

2012-05-01 | GSE34893 | GEO

MicroRNAs Regulate p21Waf1/Cip1 Protein Expression and the DNA Damage Response in Human Embryonic Stem Cells

Project description:Studies of human embryonic stem cells (hESCs) commonly describe the non-functional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs but p21 protein is not detectable. In this article, we provide evidence that expression of p21 protein is directly regulated by the microRNA pathway under standard culture conditions and after DNA damage. The DDR in hESCs leads to upregulation of tens of microRNAs, including hESC-specific microRNAs such as those of the miR-302 family, miR-371-372 family, or C19MC microRNA cluster. Most importantly, we show that the hESC-enriched microRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and thus demonstrate a novel function for miR-302s in hESCS. The described mechanism elucidates the role of microRNAs in regulation of important molecular pathway governing the G1/S transition checkpoint before as well as after DNA damage.

2015-01-01 | GSE36615 | GEO

RNA-seq profiles of rat cardiomyocytes overexpressing hsa-miR-106b-5p, hsa-miR-93-5p, hsa-miR-25-3p or cel-miR-67

Project description:Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. We report that the miR-106b~25cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. To identify the relevant targets of individual miRNAs in the miR-106b~15 cluster and elucidate the molecular mechanisms underlying the proliferative effects of this microRNA cluster, we assessed the global transcriptomic changes by deep-sequencing total neonatal mouse cardiomyocyte RNA after exogeneous transfection with hsa-miR-106b-5p, hsa-miR-93-5p, hsa-miR-25-3p and compared the transcriptomic profiles to cardiomyocytes transfected with cel-miR-67, a control miRNA.

2021-06-25 | GSE178867 | GEO

MiR-106b-25 cluster targets caspase 7 and focal adhesion in human prostate cancer

Project description:We and others previously reported that the miR-106b-25 microRNA cluster is a candidate oncogene in human prostate cancer. Here, we made the novel observation that miR-106b-25 expression is further up-regulated in distant metastasis. Moreover, increased tumor miR-106b expression was associated with early disease recurrence. To identify yet unknown oncogenic functions of the prognostic miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that caspase-7 is a candidate direct target of miR-106b, which was confirmed by Western blot analysis and a 3M-bM-^@M-^YUTR reporter assay. Other analyses showed that caspase-7 is down-regulated in primary human prostate tumors and metastatic lesions across multiple datasets and is by itself associated with disease recurrence. Using bioinformatics, we also discovered that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally confirmed using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and metastasis and may do so by altering apoptosis- and focal adhesion-related pathways. To elucidate the effects miR-106b, we up-regulated miR-106b in LNCaP cells and examined gene expression alterations on a global scale with Affymetrix arrays. LNCaP cells were transfected with pre-miR oligos and 24 hr post-transfection total RNA was collected for microarray anaylsis.

2012-04-30 | E-GEOD-34893 | biostudies-arrayexpress

TAF15 protein regulates CDKN1A through miRNAs

2012-12-21 | GSE34470 | GEO

TAF15 protein regulates CDKN1A through miRNAs

Project description:TAF15 (formerly TAFII68) is a member of the TET family of RNA and DNA binding proteins whose genes are frequently translocated in sarcomas. Consistent with a functional role in cell viability, TAF15 depletion had a growth-inhibitory effect and increased apoptosis. Interestingly, one of the genes affected by TAF15 depletion is CDKN1A/p21, a key regulator of cell cycle. Here we show that TAF15 down-regulates CDKN1A/p21 expression through a pathway involving miRNAs. We performed a gene expression profiling upon TAF15 knock down by RNA interference.Total RNAs purified from four biological replicates of HeLa GL3 luc cells transfected either with si-TAF15 or control si-LUC were hybridized to the array.

2012-12-21 | E-GEOD-34470 | biostudies-arrayexpress

Effect of miR17-92 and miR-106b-25 loss in primary calvarial cells

Project description:Gene expression profiling of primary calvarial cells with miR-17-92:miR-106b-25 conditional deletion

2019-07-04 | GSE114495 | GEO