Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression of lamina proteins Lamin and Kugelkern suppresses stem cell proliferation.

ABSTRACT: The nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological or developmental contexts. Here we investigate the role and activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies. We found that ISCs mutant for Lam or kuk proliferate, whereas overexpression of Lam or Kuk strongly suppressed proliferation. The anti-proliferative activity is, at least in part, due to suppression of Jak/Stat but not Delta/Notch signaling. Lam expression suppresses Jak/Stat signaling by normalization of about 50% of the Stat target genes in ISCs.

SUBMITTER: Petrovsky R

PROVIDER: S-EPMC5973253 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Expression of lamina proteins Lamin and Kugelkern suppresses stem cell proliferation.

Petrovsky Roman R Großhans Jörg J

Nucleus (Austin, Tex.) 20180101 1

The nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological or developmental contexts. Here we investigate the role and activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies. We found that ISCs mutant for L ...[more]

PMID: 29210315

Similar Datasets

CEBPD suppresses prolactin expression and prolactinoma cell proliferation.

Project description:Hyperprolactinemia, usually caused by a pituitary lactotroph tumor, leads to galactorrhea and infertility. Increased prolactin (PRL) levels may be due to enhanced PRL expression or proliferation of PRL-secreting cells. We hypothesize that PRL expression and PRL-secreting cell proliferation are linked. Using microarray-based gene expression profiling, we identified CCAAT-enhancer-binding protein δ (CEBPD) transcription factor as a critical gene that regulates both PRL expression and lactotroph cell proliferation. CEBPD expression levels are decreased approximately 7-fold in experimental rat prolactinoma cells. Forced expression of this transcription factor in PRL-secreting cells (GH3 and MMQ) inhibited PRL expression and cellular proliferation, and CEBPD knockdown by small interfering RNA leads to increased PRL expression in both cell lines. To determine mechanisms underlying this observation, we determined binding of CEBPD to the PRL promoter and also showed marked suppression (96%) of PRL promoter activity. CEBPD and Pit1 interact and attenuate each other's binding to the PRL promoter. CEBPD also suppresses expression of proliferation-related genes, including c-Myc, survivin, as well as cyclins B1, B2, and D1. These results show that PRL expression and cell proliferation are controlled in part by CEBPD.

| S-EPMC3198962 | biostudies-literature

The antibiotic clofoctol suppresses glioma stem cell proliferation by activating KLF13.

Project description:Gliomas account for approximately 80% of primary malignant tumors in the central nervous system. Despite aggressive therapy, the prognosis of patients remains extremely poor. Glioma stem cells (GSCs) which considered as the potential target of therapy for their crucial role in therapeutic resistance and tumor recurrence, are believed to be key factors for the disappointing outcome. Here, we took advantage of GSCs as the cell model to perform high-throughput drug screening and the old antibiotic, clofoctol, was identified as the most effective compound, showing reduction of colony-formation and induction of apoptosis of GSCs. Moreover, growth of tumors was inhibited obviously in vivo after clofoctol treatment especially in primary patient-derived xenografts (PDXs) and transgenic xenografts. The anticancer mechanisms demonstrated by analyzing related downstream genes and discovering the targeted binding protein revealed that clofoctol exhibited the inhibition of GSCs by upregulation of Kruppel-like factor 13 (KLF13), a tumor suppressor gene, through clofoctol's targeted binding protein, Upstream of N-ras (UNR). Collectively, these data demonstrated that induction of KLF13 expression suppressed growth of gliomas and provided a potential therapy for gliomas targeting GSCs. Importantly, our results also identified the RNA-binding protein UNR as a drug target.

| S-EPMC6668693 | biostudies-literature

Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins.

Project description:Lamina-associated polypeptide 2α (LAP2α) localizes throughout the nucleoplasm and interacts with the fraction of lamins A/C that is not associated with the peripheral nuclear lamina. The LAP2α-lamin A/C complex negatively affects cell proliferation. Lamins A/C are encoded by LMNA, a single heterozygous mutation of which causes Hutchinson-Gilford progeria syndrome (HGPS). This mutation generates the lamin A variant progerin, which we show here leads to loss of LAP2α and nucleoplasmic lamins A/C, impaired proliferation, and down-regulation of extracellular matrix components. Surprisingly, contrary to wild-type cells, ectopic expression of LAP2α in cells expressing progerin restores proliferation and extracellular matrix expression but not the levels of nucleoplasmic lamins A/C. We conclude that, in addition to its cell cycle-inhibiting function with lamins A/C, LAP2α can also regulate extracellular matrix components independently of lamins A/C, which may help explain the proliferation-promoting function of LAP2α in cells expressing progerin.

| S-EPMC4604344 | biostudies-literature

LIN28B suppresses microRNA let-7b expression to promote CD44+/LIN28B+ human pancreatic cancer stem cell proliferation and invasion.

Project description:Although the highly proliferative, migratory, and multi-drug resistant phenotype of human pancreatic cancer stem cells (PCSCs) is well characterized, knowledge of their biological mechanisms is limited. We used CD44 and LIN28B as markers to screen, isolate, and enrich CSCs from human primary pancreatic cancer. Using flow cytometry, we identified a human primary pancreatic cancer cell (PCC) subpopulation expressing high levels of both CD44 and LIN28B. CD44+/LIN28B+ PCSCs expressed high levels of stemness marker genes and possessed higher migratory and invasive ability than CD44-/LIN28B- PCCs. CD44+/LIN28B+ PCSCs were more resistant to growth inhibition induced by the chemotherapeutic drugs cisplatin and gemcitabine hydrochloride, and readily established tumors in vivo in a relatively short time. Moreover, microarray analysis revealed significant differences between the cDNA expression patterns of CD44+/LIN28B+ PCSCs and CD44-/LIN28B- PCCs. Following siRNA interference of endogenous LIN28B gene expression in CD44+/LIN28B+ PCSCs, not only was their proliferation decreased, there was also cell cycle arrest due to suppression of cyclin D1 expression following the stimulation of miRNA let-7b expression. In conclusion, CD44+/LIN28B+ cells, which possess CSC characteristics, can be reliably sorted from human primary PCCs and represent a valuable model for studying cancer cell physiology and multi-drug resistance.

| S-EPMC4633895 | biostudies-literature

Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis.

Project description: Not available

| S-EPMC8419681 | biostudies-literature

Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis.

Project description:The primary cilium is a sensory organelle that receives specific signals from the extracellular environment important for vertebrate development and tissue homeostasis. Lamins, the major components of the nuclear lamina, are required to maintain the nuclear structure and are involved in most nuclear activities. In this study, we show that deficiency in lamin A/C causes defective ciliogenesis, accompanied by increased cytoplasmic accumulation of actin monomers and increased formation of actin filaments. Disruption of actin filaments by cytochalasin D rescues the defective ciliogenesis in lamin A/C-depleted cells. Moreover, lamin A/C-deficient cells display lower levels of nesprin 2 and defects in recruiting Arp2, myosin Va, and tau tubulin kinase 2 to the basal body during ciliogenesis. Collectively, our results uncover a functional link between nuclear lamina integrity and ciliogenesis and implicate the malfunction of primary cilia in the pathogenesis of laminopathy.

| S-EPMC7534621 | biostudies-literature

Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis

Project description:The primary cilium is a sensory organelle that receives specific signals from the extracellular environment important for vertebrate development and tissue homeostasis. Lamins, the major components of the nuclear lamina, are required to maintain the nuclear structure and are involved in most nuclear activities. In this study, we show that deficiency in lamin A/C causes defective ciliogenesis, accompanied by increased cytoplasmic accumulation of actin monomers and increased formation of actin filaments. Disruption of actin filaments by cytochalasin D rescues the defective ciliogenesis in lamin A/C-depleted cells. Moreover, lamin A/C-deficient cells display lower levels of nesprin 2 and defects in recruiting Arp2, myosin Va and tau tubulin kinase 2 to the basal body during ciliogenesis. Collectively, our results uncover a functional link between nuclear lamina integrity and ciliogensis and implicate the malfunction of primary cilia in the pathogenesis of laminopathy.

| S-SCDT-EMBOR-2019-49680-T | biostudies-other

Knockdown of pseudogene DUXAP8 expression in glioma suppresses tumor cell proliferation.

Project description:A large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been identified as important regulators in human tumors. However, the clinical role and potential functional effects of the double homeobox A pseudogene 8 (DUXAP8) in glioma remains unknown. In the present study, it was revealed that pseudogene DUXAP8 is significantly upregulated in glioma tissues, compared with adjacent normal tissues. Patients with increased DUXAP8 expression were associated with higher Karnofsky Performance Status, advanced World Health Organization grade, poor disease-free survival and overall survival rates of patients with glioma. Furthermore, in vitro assays, Cell-Counting Kit-8 cell viability and cell colony forming assays demonstrated that reduced DUXAP8 expression significantly suppressed proliferation capacity. Therefore, the results of the present study indicate that pseudogene DUXAP8 is an oncogenic lncRNA and may serve as a potentially prognostic biomarker and novel target of glioma treatment.

| S-EPMC6396113 | biostudies-literature

Combined Poziotinib with Manidipine Treatment Suppresses Ovarian Cancer Stem-Cell Proliferation and Stemness.

Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in women worldwide, with an overall 5 year survival rate below 30%. The low survival rate is associated with the persistence of cancer stem cells (CSCs) after chemotherapy. Therefore, CSC-targeting strategies are required for successful EOC treatment. Pan-human epidermal growth factor receptor 4 (HER4) and L-type calcium channels are highly expressed in ovarian CSCs, and treatment with the pan-HER inhibitor poziotinib or calcium channel blockers (CCBs) selectively inhibits the growth of ovarian CSCs via distinct molecular mechanisms. In this study, we tested the hypothesis that combination treatment with poziotinib and CCBs can synergistically inhibit the growth of ovarian CSCs. Combined treatment with poziotinib and manidipine (an L-type CCB) synergistically suppressed ovarian CSC sphere formation and viability compared with either drug alone. Moreover, combination treatment synergistically reduced the expression of stemness markers, including CD133, KLF4, and NANOG, and stemness-related signaling molecules, such as phospho-STAT5, phospho-AKT, phospho-ERK, and Wnt/β-catenin. Moreover, poziotinib with manidipine dramatically induced apoptosis in ovarian CSCs. Our results suggest that the combinatorial use of poziotinib with a CCB can effectively inhibit ovarian CSC survival and function.

| S-EPMC7583017 | biostudies-literature

Nuclear lamina dysfunction triggers a germline stem cell checkpoint.

Project description:LEM domain (LEM-D) proteins are conserved components of the nuclear lamina (NL) that contribute to stem cell maintenance through poorly understood mechanisms. The Drosophila emerin homolog Otefin (Ote) is required for maintenance of germline stem cells (GSCs) and gametogenesis. Here, we show that ote mutants carry germ cell-specific changes in nuclear architecture that are linked to GSC loss. Strikingly, we found that both GSC death and gametogenesis are rescued by inactivation of the DNA damage response (DDR) kinases, ATR and Chk2. Whereas the germline checkpoint draws from components of the DDR pathway, genetic and cytological features of the GSC checkpoint differ from the canonical pathway. Instead, structural deformation of the NL correlates with checkpoint activation. Despite remarkably normal oogenesis, rescued oocytes do not support embryogenesis. Taken together, these data suggest that NL dysfunction caused by Otefin loss triggers a GSC-specific checkpoint that contributes to maintenance of gamete quality.

| S-EPMC6160405 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data