Gene expression analysis to identify target genes of miR-150 in Hodgkin lymphoma cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE188310 | GEO | 2021/11/06
REPOSITORIES: GEO
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Project description:The oncogenic transcription factor MYC regulates expression of protein-coding genes, microRNAs and long non-coding RNAs. Here we show that overexpression of the MYC-repressed miR-150 severely impaired growth of Burkitt lymphoma (BL) cells. AGO2-RIP-Chip revealed two novel miR-150 targets, ZDHHC11 and ZDHHC11B, as the two most enriched genes, followed by MYB, a known miR-150 target. ZDHHC11 and ZDHHC11B encode both protein-coding and non-coding transcripts and contain a strikingly high number of miR-150 binding sites, i.e. 18 and 62, respectively. Effective targeting of ZDHHC11 and ZDHHC11B by miR-150 was confirmed by luciferase assay and for the ZDHHC11 protein by Western blot. Furthermore, we identified a circular ZDHHC11 transcript which contains the miR-150 binding site region and interacts strongly with miR-150. Knockdown of both MYB and ZDHHC11/ZDHHC11B significantly impaired growth of BL cells. Moreover, downregulation of ZDHHC11/ZDHHC11B also resulted in reduced MYB levels in BL cells. Together, our results demonstrate that elevated levels of MYB required for the high proliferative state of BL cells are ensured in two ways. First, MYC represses the tumor suppressor miR-150, which prevents its inhibitory effects on MYB expression. Second, the novel miR-150 targets ZDHHC11 and ZDHHC11B are required for maintaining high MYB levels in BL cells.
2017-03-24 | GSE86432 | GEO
Project description:In Burkitt lymphoma (BL), a network consisting of MYC, MYC-repressed miR-150 and miR-150 targets MYB and ZDHHC11 has been established. This network plays an important role on the growth of BL cells. Here, we performed gene expression analysis to identify targets of ZDHHC11.
2024-01-01 | GSE218286 | GEO
Project description:MYC regulates the expression of multiple microRNA (miRNA) genes and defines the Burkitt lymphoma (BL) miRNA signature. Here, we investigate the role of the MYC-regulated miRNAs by gain- and loss-of-function analysis. Overexpression of 5 miRNAs that were significantly downregulated by MYC resulted in strong (miR-150, miR-26a, miR-26b) and mild (miR-29a, let-7a) impaired cell growth. Overexpression of miR-155 increased proliferation of BL cells. By RNA immunoprecipitation of Argonaute 2 in BL cells with and without miR-155 we identified 54 miR-155 target genes. Using an shRNA approach we identified TBRG1 (NIAM1) as a miR-155 target gene that copied the miR-155-induced phenotype upon its inhibition. Analysis of TBRG1 protein expression and miR-155 levels in primary cases of B-cell lymphoma revealed that miR-155 levels are significantly lower in TBRG1 positive cases suggesting that TBRG1 is also regulated by miR-155 in primary B-cell lymphoma. Our data demonstrate that overexpression of individual MYC-repressed miRNAs has a strong suppressive effect on BL cell growth, whereas overexpression of miR-155 enhances B-cell lymphoma growth by targeting the tumor suppressor gene TBRG1. Gene expression profile was performed in ST486 Burkitt lymphoma cell line in 4 samples: ST486 EV (empty MXW-PGK-IRES-GFP vector) total cell lysate, ST486 EV Ago2-IP, ST486 miR-155 (ST486 with ectopic miR-155) total cell lysate, ST486 miR-155 Ago2-IP.
2015-02-20 | E-GEOD-64484 | biostudies-arrayexpress
Project description:We examined the function of miR-150 in T-cell lymphomagenesis. We transfected GFP-control or GFP-miR-150 into several T-cell lymphoma lines and sought which genes were regulated by miR-150.
2013-07-30 | GSE49308 | GEO
Project description:We examined the function of miR-150 in T-cell lymphomagenesis. We transfected GFP-control or GFP-miR-150 into several T-cell lymphoma lines and sought which genes were regulated by miR-150. To examine the function of miR-150 in T-cell lymphomagenesis, we first transfected GFP-control (Mock) or GFP-miR-150 into several T-cell lymphoma lines (ATN-1, HUT78, My-La, and HH). To detect genes commonly downregulated among these cells, we used the CodeLinkTM Human Whole Genome Bioarray platform with the criterion that the miR-150/GFP-control ratio must be <0.75 in all 3 CTCL lines.
2013-07-30 | E-GEOD-49308 | biostudies-arrayexpress
Project description:Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma (B-NHL), which originates from germinal center (GC) B cells and harbors translocations deregulating the MYC oncogene. A comparative analysis of microRNAs (miRNAs) expressed in normal and malignant GC B cells identified miR-28 as significantly down-regulated in BL, as well as in other GC-derived B-NHL. We show that re-expression of miR-28 impairs cell growth and clonogenic properties of BL cells by modulating several targets including MAD2L1, a component of the spindle checkpoint whose down-regulation is essential in mediating miR-28-induced growth-arrest, and BAG1, an activator of the ERK pathway.
2014-06-01 | GSE56268 | GEO
Project description:c-myc-3'RR mice prone to develop Burkitt lymphoma (BL) were crossed with p53+/- mice in order to obtain c-myc-3'RR/p53+/- mice. These mice develop a wider spectrum of lymphoma including BL, mantle cell lymphoma (MCL) and plasma cell lymphoma (PCL). Transcriptoma analysis of these lymphomas is investigated in these arrays.
2012-01-05 | GSE31814 | GEO
Project description:Glucocorticoids (GCs) are commonly used to treat patients suffering from lymphoid malignancies i.e. leukemia and multiple myeloma. Although GCs are known to be strong inducers of apoptosis in lymphoid cells, the molecular determinants of GC therapy resistance are poorly understood. Although GC treatment triggers important changes in gene expression, few studies have addressed the regulatory role of small regulatory microRNAs (miRNAs) in GC therapy response. Only recently, aberrant microRNA expression has been linked to the development of haematological malignancies and microRNAs have become master regulators of drug resistance. We identified GC inducible mRNA and microRNA transcription profiles in GC sensitive MM1S as compared to GC resistant MM1R cells. Transcriptome analysis revealed that GCs regulate multiple genes involved in cell cycle control, cell organization and cell death in MM1S, which remain unaffected in MM1R cells. Correspondingly, GCs selectively trigger cell death in MM1S but not in MM1R. Out of 32 microRNAs responsive to GC in MM1S cells but not in MM1R cells, mir-150 was identified as the most persistent GC responsive microRNA. Furthermore, Ingenuity Pathways Analysis (IPA) revealed that ectopic transfection of a synthetic mir-150 mimics GC therapy response in MM1S cells, associated with selective changes in mRNA levels of typical GR transactivated and transrepressed target genes. Although mir-150 largely mirrors GC responsive changes in gene expression of the transcription factor Myb, GR chaperone FKBP5, cell cycle modulator proteins (IL23A, SKP2, CDKN1A), chemokine signaling proteins (CXCR4, CX3CR1, CCL3) and mTOR/UPR stress related proteins (DDIT4, TXNIP), we also observed mir-150 selective effects on transcription factors (NR3C2 (MR), Myb, Fos, Jun, C/EBP-beta, IRF4, NFE2L1, ATF3, ATF4,), chaperone molecules HSPA8, HSP90AB1), the sodium channel SCNN1G and UPR stress proteins (TRIB3, DDIT3). Remarkably, mir-150 overexpression was not able to overcome GC therapy resistance, since we could not detect GC like effects of mir-150 in GR (NR3C1) deficient MM1R cells. Altogether GC-inducible mir-150 adds a novel complex layer of regulation for fine tuning GC specific therapeutic responses in multiple myeloma.
2014-12-01 | GSE59805 | GEO
Project description:Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma (B-NHL), which originates from germinal center (GC) B cells and harbors translocations deregulating the MYC oncogene. A comparative analysis of microRNAs (miRNAs) expressed in normal and malignant GC B cells identified miR-28 as significantly down-regulated in BL, as well as in other GC-derived B-NHL. We show that re-expression of miR-28 impairs cell growth and clonogenic properties of BL cells by modulating several targets including MAD2L1, a component of the spindle checkpoint whose down-regulation is essential in mediating miR-28-induced growth-arrest, and BAG1, an activator of the ERK pathway. P3HR1 Burkitt lymphoma cell line was engineered to display inducible expression of GFP alone or GFP in combination with the miR-28 precursor from the pRTS1 vector upon doxycycline treatment. Two bulk populations (A and B) were established for both the control (GFP alone) and the miR28-expressing (GFP and miR-28 precursor) cells. Cells were induced with 0.1ug/ml doxycycline for 12h or 24h. Induction was performed on each bulk population in triplicates.
2014-06-01 | E-GEOD-56268 | biostudies-arrayexpress
Project description:Gene expression analysis to identify target genes of miR-150 in Hodgkin lymphoma cell lines
| PRJNA778243 | ENA