Similar Datasets
Project description:Multiple myeloma (MM) is the second most prevalent hematological malignancy that carries a poor prognosis. Despite significant advances in new treatments, most patients relapse due to the high genetic heterogeneity leading to treatment resistance. Recurrent mutations causing hyperactivation of the non-canonical NF-ĸB pathway are frequently enriched in relapsed, refractory MM patients, contributing to disease severity and drug resistance. Here, to identify NF-ĸB targets involved in chemoresistance, we combined multi-modal analysis of the NF-ĸB/p52 regulated myeloma epigenome with patient transcriptomics and uncovered a long non-coding RNA (lncRNA) linked to treatment resistant MM patients. The lncRNA termed PLUM is overexpressed in NF-ĸB+ high-risk MM subtypes and patients who are refractory to VRd (Bortezomib-Lenalidomide-Dexamethasone) treatment regimen. We reveal that PLUM interacts with Polycomb repressive complex 2 (PRC2) to regulate its stability and histone methyltransferase activity. Notably, PLUM binds to the disordered region of PRC2 subunit EZH2, modulating the expression of tumor suppressor genes, FOXO3 and ZFP36, to activate the unfolded protein response (UPR). Disruption of PLUM-EZH2 interaction using steric antisense oligonucleotides re-sensitized myeloma tumor cells to drug treatment, correlating with the loss of PRC2 stability and EZH2 H3K27 trimethylation activity. These findings indicate NF-ĸB/p52 regulated lncRNA, PLUM, modulates the myeloma epigenome by facilitating formation of PRC2 complex and EZH2 activity to mediate chemoresistance. Targeting specific PLUM-EZH2 interactions may represent a clinically important strategy for the treatment of relapsed, refractory MM.
2025-06-30 | GSE274151 | GEO
Project description:Plum Island Sub-millimeter scale microbial analysis Metagenome
| PRJNA347837 | ENA
Project description:Orthotopic tumors were previously generated from parental Prostate Luminal (PLum) cells under androgen‑dependent (PLum-AD) and androgen‑independent (PLum-AI) conditions in order to establish cellular models of prostate cancer progression (Abou-Kheir et al., 2011; doi: 10.1371/journal.pone.0026112). We used microarrays to evaluate the differential gene expression profiles underlying progression of prostate cancer from primary androgen-dependent stage to advanced androgen-independent stage using newly isolated murine prostate cancer cell lines. Those cell lines represent novel in vitro models of androgen‑dependent and –independent prostate cancer, recapitulating the progression of the disease to a more invasive phenotype upon androgen deprivation.
2020-05-27 | GSE151187 | GEO
Project description:Multiple myeloma (MM) is the second most prevalent hematological malignancy that carries a poor prognosis. Despite significant advances in new treatments, most patients relapse due to the high genetic heterogeneity leading to treatment resistance. Recurrent mutations causing hyperactivation of the non-canonical NF-ĸB pathway are frequently enriched in relapsed, refractory MM patients, contributing to disease severity and drug resistance. Here, to identify NF-ĸB targets involved in chemoresistance, we combined multi-modal analysis of the NF-ĸB/p52 regulated myeloma epigenome with patient transcriptomics and uncovered a long non-coding RNA (lncRNA) linked to treatment resistant MM patients. The lncRNA termed PLUM is overexpressed in NF-ĸB+ high-risk MM subtypes and patients who are refractory to VRd (Bortezomib-Lenalidomide-Dexamethasone) treatment regimen. We reveal that PLUM interacts with Polycomb repressive complex 2 (PRC2) to regulate its stability and histone methyltransferase activity. Notably, PLUM binds to the disordered region of PRC2 subunit EZH2, modulating the expression of tumor suppressor genes, FOXO3 and ZFP36, to activate the unfolded protein response (UPR). Disruption of PLUM-EZH2 interaction using steric antisense oligonucleotides re-sensitized myeloma tumor cells to drug treatment, correlating with the loss of PRC2 stability and EZH2 H3K27 trimethylation activity. These findings indicate NF-ĸB/p52 regulated lncRNA, PLUM, modulates the myeloma epigenome by facilitating formation of PRC2 complex and EZH2 activity to mediate chemoresistance. Targeting specific PLUM-EZH2 interactions may represent a clinically important strategy for the treatment of relapsed, refractory MM.
2025-06-30 | GSE274078 | GEO
Project description:Prunus persica (peach) trees carrying the ‘Pillar’ or ‘Broomy’ trait (br) have vertically oriented branches caused by loss of function mutations in a gene called TILLER ANGLE CONTROL 1 (TAC1). TAC1 encodes a protein in the IGT gene family that includes LAZY1 and DEEPER ROOTING 1 (DRO1), which regulat lateral branch and root orientations, respectively. Here, we found that some of the native TAC1 alleles in the hexaploid plum species Prunus domestica, which has a naturally more upright stature, contained a variable length trinucleotide repeat within the same exon 3 region previously found to be disrupted in pillar peach trees. RNAi silencing of TAC1 in plum resulted in trees with severely vertical branch orientations similar to those in pillar peaches but with an even narrower profile. In contrast, PpeTAC1 over-expression in plum led to trees with wider branch angles and more horizontal branch orientations. Pillar peach trees and transgenic plum lines exhibited pleiotropic phenotypes including differences in trunk and branch diameter, stem growth, and twisting branch phenotypes. Expression profiling of pillar peach trees revealed differential expression of numerous genes associated with biotic and abiotic stress, hormone responses, plastids, reactive oxygen, and secondary and cell wall metabolism. Collectively, the data provide important clues for understanding TAC1 function and show that alteration of TAC1 expression may have broad applicability to agricultural and ornamental tree industries.
2018-04-04 | GSE112649 | GEO
Project description:Multiple myeloma (MM) ranks the second most prevalent haematological malignancy globally. Despite advancements in managing MM, it remains incurable due to the high genetic heterogeneity leading to treatment resistance and disease severity. One key drug resistance associated signalling pathway often hyperactivated in MM patients is the non-canonical NF- κB/p52 pathway. Additionally, dysregulated expression of various oncogenic long non-coding RNAs (lncRNAs) have been observed in MM. This study aims to examine the potential link between ncNF-κB activation and dysregulated lncRNA expression controlling the chemoresistance and oncogenic progression of MM. Using mutant MM cell lines as model system and omics data from MM patients, we identified a novel p52 regulated lncRNA enriched in high-risk MM patients. The lncRNA termed PLUM (PRC2 associated LncRNA regulating UPR in MM) is found to interact directly with PRC2 complex to mediate myeloma progression and chemoresistance. RACE (Rapid amplification of cDNA ends) analysis revealed PLUM exists in three main isoforms in drug resistant multiple myeloma cell lines (MMCLs), comprising 8 exons without coding potential. Functionally, PLUM exerts its oncogenic and drug resistance properties in vivo and in vitro via the activation of unfolded protein response (UPR) pathway. This is consistent with its elevated expression in VRd (Bortezomib- Lenalidomide-Dexamethasone) non-responsive MM patients. PLUM localizes predominantly in the nucleus where it interacts directly with the disordered region of EZH2 (489-494 aa residues) to facilitate formation of the PRC2 complex and EZH2 activity. Disruption of this interaction using steric antisense oligonucleotides (ASOs) re-sensitized MMCLs to drug treatment in vitro and in vivo, correlating with the loss of EZH2 H3K27 trimethylation activity and PRC2 complex stability. Finally, we demonstrate that PLUM-EZH2 regulates the expression of tumour suppressor genes, FOXO3 and ZFP36, to activate the UPR pathway and promote chemoresistance in MM. These findings indicate that ncNF-κB pathway regulated lncRNA PLUM is oncogenic, acting through the PRC2/FOXO3/ZFP36 axis to confer chemoresistance in MM.
2025-06-23 | PXD054586 | Pride
Project description:Many Luminal breast cancers are heterogeneous, containing substantial numbers of estrogen (ER-) and progesterone (PR-) receptor-negative cells among the ER+PR+ ones. Currently, the Basal-like ER-PR- Luminobasal subpopulation in Luminal disease is not targeted for treatment. To address the relationships between ER+PR+ and ER-PR- cells in Luminal cancers and tightly control their ratios, we have generated isogenic pure Luminal (pLUM) and pure Luminobasal (pLB) cells from the same parental Luminal human breast cancer cell line. We show that pLUM suppress proliferation of pLB cells in mixed-cell 3D colonies in vitro and in pLUM:pLB mixed-cell xenografts in mice. High-throughput screening of FDA-approved oncology drugs reveal pLB cells are sensitive to the EGFR inhibitors Gefitinib and Erlotinib. In mixed-cell 3D colonies and mixed-cell solid mouse tumors, combination therapy with the antiestrogen Fulvestrant and the EGFRi Gefitinib constitutes a robust treatment strategy. We propose that response to combination endocrine/EGFRi therapies in heterogeneous Luminal cancers will improve long-term survival in patients whose primary tumors have been preselected for the appropriate biomarkers.
2014-07-14 | GSE55350 | GEO
Project description:This DATASET collection includes the mass spectrometry files for proteomics venom investigation of island and mainland V. ammodytes populations from North Macedonia.
Sample list:
1. Island - adult - male
2. Island - adult - female
3. Island - juvenile
4. Island - subadult
5. Mainland - adult
6. Mainland - subadult
7. Mainland - juvenile
Folders 01-07 - BOTTOM-UP PROTEOMICS: The venom pools were investigated by the bottom-up "snake venomics" (labelled as SVX) approach and in short: separated by RP-HPLC, followed by SDS-PAGE separation and the single bands were in-gel processed by DTT, IAC and finally o/n tryptic digested. Samples submitted to HPLC-MS/MS. Early peptidic fractions of the first HPLC run were directly submitted to HPLC-MS/MS analytic w/o further gel procession. Folders 01 to 07 include the MS and MS/MS spectra of the V. ammodytes sample pools from different populations. Files are included as RAW and MZML format.
Used instrument: LTQ Orbitrap XL mass spectrometer (Thermo, Bremen, Germany) with an Agilent 1260 HPLC system (Agilent Technologies, Waldbronn, Germany) using a reversed-phase Grace Vydac 218MS C18 (2.1 x 150 mm; 5 um particle size) column.
Modifications: UNIMOD:4 - \"Iodoacetamide derivative.\"
Used protein database: Uniprot_8750_serpentes_CanNIso_2674_entries_220210_cRAP_220210.fasta
2024-06-18 | MSV000095060 | MassIVE