Similar Datasets
Project description:Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here, we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of cerebellar degeneration-related 1 antisense (CDR1as), a regulator of miR-7, as a hallmark of melanoma progression. CDR1as depletion results from epigenetic silencing of LINC00632, its originating long non-coding RNA (lncRNA) and promotes invasion in vitro and metastasis in vivo through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as levels reflect cellular states associated with distinct therapeutic responses. Our study reveals functional, prognostic, and predictive roles for CDR1as and expose circRNAs as key players in metastasis.
| S-EPMC7184928 | biostudies-literature
Project description:Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of Cerebellar Degeneration Related 1 (CDR1as), a regulator of the microRNA miR-7, as a hallmark of melanoma progression. We find that CDR1as depletion results from epigenetic silencing of its originating lincRNA, and promotes invasion in vitro and metastasis in vivo, through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as levels identify cellular states associated with distinct therapeutic responses. Our study reveals functional, prognostic and predictive roles for CDR1as and expose circRNAs as key players in metastasis.
2020-01-13 | GSE138412 | GEO
Project description:Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of Cerebellar Degeneration Related 1 (CDR1as), a regulator of the microRNA miR-7, as a hallmark of melanoma progression. We find that CDR1as depletion results from epigenetic silencing of its originating lincRNA, and promotes invasion in vitro and metastasis in vivo, through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as levels identify cellular states associated with distinct therapeutic responses. Our study reveals functional, prognostic and predictive roles for CDR1as and expose circRNAs as key players in metastasis.
2020-01-13 | GSE138710 | GEO
Project description:Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis
| PRJNA576880 | ENA
Project description:Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis [RNA-Seq]
| PRJNA576209 | ENA
Project description:Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis [RIP-Seq]
| PRJNA576884 | ENA
Project description:Aberrant epigenetic transcriptional regulation is linked to metastasis, a primary cause of cancer-related death. Dissecting the epigenetic mechanisms controlling metastatic progression may uncover important insights to tumor biology and potential therapeutic targets. Here, we investigated the role of the SIN3A histone deacetylase 1 and 2 (SIN3A-HDAC1/2) complex in cancer metastasis. Using a mouse model of melanoma metastasis, we found that the SIN3A-HDAC1/2 transcription repressor complex silences BMP6 expression, causing increased metastatic dissemination and tumor growth via suppression of BMP6-activated SMAD5 signaling. We further discovered that FAM83G/PAWS1, a downstream effector of BMP6-SMAD5 signaling, contributes critically to metastatic progression by promoting actin-dependent cytoskeletal dynamics and cell migration. Pharmacologic inhibition of the SIN3A-HDAC1/2 complex reduced the numbers of melanoma cells in the circulation and inhibited metastatic tumor growth by inducing disseminated cell dormancy, highlighting the SIN3A-HDAC1/2 repressor complex as a potential therapeutic target for blocking cancer metastasis. IMPLICATIONS: This study identifies the novel molecular links in the metastatic progression to target cytoskeletal dynamics in melanoma and identifies the SIN3A-HDAC1/2 complex and FAM83G/PAWS1 as potential targets for melanoma adjuvant therapy.
| S-EPMC9744461 | biostudies-literature
Project description:BackgroundThe transforming growth factor-beta (TGF-beta) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-beta signaling.MethodsWe used real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine GLI2 expression in human melanoma cell lines and subsequently classified them as GLI2high or as GLI2low according to their relative GLI2 mRNA and protein expression levels. GLI2 expression was reduced in a GLI2high cell line with lentiviral expression of short hairpin RNA targeting GLI2. We assessed the role of GLI2 in melanoma cell invasiveness in Matrigel assays. We measured secretion of matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography and expression of E-cadherin by western blotting and RT-PCR. The role of GLI2 in development of bone metastases was determined following intracardiac injection of melanoma cells in immunocompromised mice (n = 5-13). Human melanoma samples (n = 79) at various stages of disease progression were analyzed for GLI2 and E-cadherin expression by immunohistochemistry, in situ hybridization, or RT-PCR. All statistical tests were two-sided.ResultsAmong melanoma cell lines, increased GLI2 expression was associated with loss of E-cadherin expression and with increased capacity to invade Matrigel and to form bone metastases in mice (mean osteolytic tumor area: GLI2high vs GLI2low, 2.81 vs 0.93 mm(2), difference = 1.88 mm(2), 95% confidence interval [CI] = 1.16 to 2.60, P < .001). Reduction of GLI2 expression in melanoma cells that had expressed high levels of GLI2 substantially inhibited both basal and TGF-beta-induced cell migration, invasion (mean number of Matrigel invading cells: shGLI2 vs shCtrl (control), 52.6 vs 100, difference = 47.4, 95% CI = 37.0 to 57.8, P = .024; for shGLI2 + TGF-beta vs shCtrl + TGF-beta, 31.0 vs 161.9, difference = -130.9, 95% CI = -96.2 to -165.5, P = .002), and MMP secretion in vitro and the development of experimental bone metastases in mice. Within human melanoma lesions, GLI2 expression was heterogeneous, associated with tumor regions in which E-cadherin was lost and increased in the most aggressive tumors.ConclusionGLI2 was directly involved in driving melanoma invasion and metastasis in this preclinical study.
| S-EPMC2914763 | biostudies-literature
Project description:Enhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2). EZH2 overexpression inhibited TIMP2 expression and promoted proteolytic activities of matrix metalloproteinases 2 and 9 and vice versa. EZH2 promoted ovarian cancer invasion and migration, which could be largely reversed by TIMP2 down-regulation in vitro and in vivo. Both H3K27me3 inhibition and demethylation could reduce methylation of the TIMP2 promoter and finally reactivate TIMP2 transcription. The presence of EZH2 and H3K27me3 at the TIMP2 promoter was confirmed by chromatin immunoprecipitation. H3K27me3 and DNA methyltransferases at the promoter were significantly increased by EZH2 overexpression. These results suggest that EZH2 inhibits TIMP2 expression via H3K27me3 and DNA methylation, which relieve the repression of MMP and facilitate ovarian cancer invasion and migration.
| S-EPMC5472630 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-06-29 | GSE162364 | GEO