Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA158405 | ENA |
REPOSITORIES: ENA
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Project description:miR-93/106b and their host gene minichromosome maintenance complex component 7 (MCM7) reside at chr7q22, a region frequently rearranged in leiomyomas. We explored the expression of miR-93/106b in leiomyoma and paired myometrium (N=62) from untreated and patients exposed to hormonal therapies (GnRHa, Depo-Provera and oral contraceptives) from African Americans and Caucasians, and their regulatory functions in isolated paired (N=15) leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1). At tissue level leiomyomas expressed significantly lower levels of miR-93 and elevated MCM7 as compared to myometrium with limited racial influence or hormonal exposure on their expression. Assessing the regulatory function of miR-93/106b through doxycycline-inducible lentiviral transduction in microarray analysis, tissue factor (F3) and IL-8 were identified as their possible targets. At tissue level leiomyomas expressed a significantly lower level of F3 and an elevated IL-8 which exhibited an inverse relationship with miR-93, but with limited racial or hormonal influences. Gain-of-function of miR-93/106b in LSMC, MSMC and SKLM-S1 dose-dependently repressed F3 and IL-8 through direct interactions with their respective 3M-bM-^@M-^YUTRs and indirectly through F3 repression inhibited IL8, CTGF and PAI-1 expression, confirmed by using siRNA silencing or factor Vlla (FVIIa) activation of F3, as well as reducing the rate of proliferation, while increasing caspase 3/7 activity. We concluded that differential expression of miR-93/106b and their direct and/or indirect regulatory functions on F3, IL-8, CTGF and PAI-1 expression, with key roles in inflammation and tissue turnover may be of significance in the outcome of leiomyoma growth and associated symptoms. Total RNA isolated from TF324 cells transfected with DOX-inducible lentiviral construct carrying miR-106b~25 cluster with and without Dox treatments for 6 days was subjected to gene expression profiling using Sentirx Beadchip Array HumanHT-12_v4.
2012-04-09 | E-GEOD-37122 | biostudies-arrayexpress
Project description:miR-93/106b and their host gene minichromosome maintenance complex component 7 (MCM7) reside at chr7q22, a region frequently rearranged in leiomyomas. We explored the expression of miR-93/106b in leiomyoma and paired myometrium (N=62) from untreated and patients exposed to hormonal therapies (GnRHa, Depo-Provera and oral contraceptives) from African Americans and Caucasians, and their regulatory functions in isolated paired (N=15) leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1). At tissue level leiomyomas expressed significantly lower levels of miR-93 and elevated MCM7 as compared to myometrium with limited racial influence or hormonal exposure on their expression. Assessing the regulatory function of miR-93/106b through doxycycline-inducible lentiviral transduction in microarray analysis, tissue factor (F3) and IL-8 were identified as their possible targets. At tissue level leiomyomas expressed a significantly lower level of F3 and an elevated IL-8 which exhibited an inverse relationship with miR-93, but with limited racial or hormonal influences. Gain-of-function of miR-93/106b in LSMC, MSMC and SKLM-S1 dose-dependently repressed F3 and IL-8 through direct interactions with their respective 3’UTRs and indirectly through F3 repression inhibited IL8, CTGF and PAI-1 expression, confirmed by using siRNA silencing or factor Vlla (FVIIa) activation of F3, as well as reducing the rate of proliferation, while increasing caspase 3/7 activity. We concluded that differential expression of miR-93/106b and their direct and/or indirect regulatory functions on F3, IL-8, CTGF and PAI-1 expression, with key roles in inflammation and tissue turnover may be of significance in the outcome of leiomyoma growth and associated symptoms.
2012-04-10 | GSE37122 | GEO
Project description:MicroRNAs are small non-coding RNAs that regulate mRNA function. Recent studies have shown that microRNA expression is altered in tumors. We studied the expression of both microRNAs and mRNAs in 60 primary prostate tumors and 16 non-tumor prostate tissues to evaluate the involvement of microRNAs in prostate cancer. Global microRNA expression was determined in RNA isolated from fresh-frozen human tissues with a custom oligonucleotide microarray chip. Expression analysis of mRNAs using Affymetrix gene chips revealed that Dicer, a key component of microRNA processing, and two microRNA host genes, MCM7 and C9orf5, were significantly up-regulated in prostate tumors. Consistent with the findings, tumors expressed at higher levels the miR-25 cluster (miR-25/miR-93/miR-106b), which maps to intron 13 of MCM7, and miR-32, which maps to intron 14 of C9orf5, than non-tumor prostate tissues. Other microRNAs that were overexpressed included miR-26a, miR-31, miR-182, miR-196a, and miR-200c, among others, and homologues of the miR-25 cluster, such as miR-92 and miR-106a. Among the down-regulated microRNAs in tumors were the miR-1/miR-133a cluster, miR-490, miR-494 and miR-520h. Differences in microRNA expression were also observed between high and low Gleason score and between tumors that either showed or did not show extraprostatic extension. A 37-probeset signature, representing 23 different mature microRNAs, correctly classified all non-tumor tissues and 80% of the tumors. In summary, our data indicate that alterations in microRNA expression occur in the development and progression of human prostate cancer. Such changes may prove useful in the development of novel diagnostic and prognostic markers. Keywords: Marcodissected tissues
2008-08-06 | GSE8126 | GEO
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
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
Project description:MicroRNAs are small non-coding RNAs that regulate mRNA function. Recent studies have shown that microRNA expression is altered in tumors. We studied the expression of both microRNAs and mRNAs in 60 primary prostate tumors and 16 non-tumor prostate tissues to evaluate the involvement of microRNAs in prostate cancer. Global microRNA expression was determined in RNA isolated from fresh-frozen human tissues with a custom oligonucleotide microarray chip. Expression analysis of mRNAs using Affymetrix gene chips revealed that Dicer, a key component of microRNA processing, and two microRNA host genes, MCM7 and C9orf5, were significantly up-regulated in prostate tumors. Consistent with the findings, tumors expressed at higher levels the miR-25 cluster (miR-25/miR-93/miR-106b), which maps to intron 13 of MCM7, and miR-32, which maps to intron 14 of C9orf5, than non-tumor prostate tissues. Other microRNAs that were overexpressed included miR-26a, miR-31, miR-182, miR-196a, and miR-200c, among others, and homologues of the miR-25 cluster, such as miR-92 and miR-106a. Among the down-regulated microRNAs in tumors were the miR-1/miR-133a cluster, miR-490, miR-494 and miR-520h. Differences in microRNA expression were also observed between high and low Gleason score and between tumors that either showed or did not show extraprostatic extension. A 37-probeset signature, representing 23 different mature microRNAs, correctly classified all non-tumor tissues and 80% of the tumors. In summary, our data indicate that alterations in microRNA expression occur in the development and progression of human prostate cancer. Such changes may prove useful in the development of novel diagnostic and prognostic markers. Keywords: Marcodissected tissues Sixty fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the frozen specimens. Surrounding non-tumor prostate tissue was collected from 16 patients with prostate cancer. All tissues were collected between 2002 and 2004. Information on race/ethnicity was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire (UMD). Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. The study was approved by the institutional review boards of the participating institutions. Total RNA was isolated using the TRIZOL reagent according to the manufacturer’s instructions (Invitrogen, Carlsbad, CA). RNA integrity for each sample was confirmed with the Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). Each RNA was then split into two pools that were either processed for the microRNA microarray or the mRNA microarray.
2008-08-05 | E-GEOD-8126 | biostudies-arrayexpress
Project description:We have generated a miR-17~92 fl/fl allele whose expression can be turned off conditionally by Cre recombinase in the miR-106a-363-/-;miR-106b-25-/- background. The mice were crossed to CD19-Cre mice to turn off the expression of miR-17~92 specifically in B cells and stimulated LPS/IL-4 for 13.5hr. Follicular B(FoB) cells were purified from CD19-Cre;miR-17~92 fl/fl;miR-106a-363;miR-106b~25 mice (TKO1, TKO2, TKO3) and WT (WT1, WTl2, WT3) by MACS depletion of cells positive for CD9, CD43, and CD93 (also known as AA4.1). The purified B cells were stimulated with LPS/IL-4 for 13.5hr in B cell media. The purity of follicular B cells was examined by flow cytometry and was greater than 95% for all samples. Total RNA was extracted using RNeasy kit (QIAGEN).
2014-04-01 | E-GEOD-56378 | biostudies-arrayexpress
Project description:Despite progesterone’s key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. The aim of this study was to identify novel gene products mediating progesterone’s effects in uterine leiomyomas. Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro. Our analyses identified secreted frizzled-related protein 4 (sFRP4) as a key gene product functionally linked to PR activation whose expression was a) 2.6-fold higher in leiomyomas than myometrium (n=26, p<0.01) and b) 2.5-fold higher during the proliferative phase of the menstrual cycle (n=26, p<0.01).
2018-06-06 | GSE95101 | GEO
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
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