Similar Datasets
Project description:Brain metastasis is a major cause of cancer mortality, but its molecular mechanisms are severely understudied. In addition, little is known regarding the role of m6A reader YTHDF3 in human diseases. Here, we show that YTHDF3 overexpression clinically correlates with brain metastases in breast cancer patients. YTHDF3 promotes cancer cell interactions with brain endothelial cells and astrocytes, blood-brain barrier extravasation, angiogenesis, and outgrow. Mechanistically, YTHDF3 enhances the translation of m6A-enriched transcripts for ST6GALNAC5, GJA1, and EGFR, all associated with brain metastasis. Furthermore, overexpression of YTHDF3 in brain metastases is attributed to increased gene copy number and the autoregulation of YTHDF3 cap-independent translation by binding to m6A residues within its own 5' UTR. Our work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby inducing brain metastatic competence.
| S-EPMC7738369 | biostudies-literature
Project description:Brain metastasis is a major cause of cancer mortality, but its molecular mechanisms are severely understudied. We found that YTHDF3 overexpression clinically correlates with brain metastases in breast cancer patients and is required for brain metastasis. Silencing YTHDF3 suppressed the brain metastasis of breast cancer cells in vitro and in vivo. Integrated transcriptome and m6A-seq analysis revealed alter expression of selected YTHDF3 target genes, including ST6GALNAC5, GJA1, and EGFR by promoting m6A-dependent translation of these target transcripts. Our work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby gaining brain metastatic competence.
2020-09-30 | GSE130172 | GEO
Project description:Brain metastasis is a major cause of cancer mortality, but its molecular mechanisms are severely understudied. We found that YTHDF3 overexpression clinically correlates with brain metastases in breast cancer patients and is required for brain metastasis. Silencing YTHDF3 suppressed the brain metastasis of breast cancer cells in vitro and in vivo. Integrated transcriptome and m6A-seq analysis revealed alter expression of selected YTHDF3 target genes, including ST6GALNAC5, GJA1, and EGFR by promoting m6A-dependent translation of these target transcripts. Our work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby gaining brain metastatic competence.
2020-09-30 | GSE130171 | GEO
Project description:YTHDF3 Induces the Translation of m6A-enriched Metastasis-associated Gene Transcripts to Promote Breast Cancer Brain Metastasis
| PRJNA534211 | ENA
Project description:YTHDF3 Induces the Translation of m6A-enriched Metastasis-associated Gene Transcripts to Promote Breast Cancer Brain Metastasis [m6A-seq]
| PRJNA534214 | ENA
Project description:YTHDF3 Induces the Translation of m6A-enriched Metastasis-associated Gene Transcripts to Promote Breast Cancer Brain Metastasis [RIP-Seq]
| PRJNA534213 | ENA
Project description:Peroxiredoxin 3 (PRDX3) acts as a master regulator of mitochondrial oxidative stress and exerts hepatoprotective effects, but the role of PRDX3 in liver fibrosis is not well understood. N6-methyladenosine (m6A) is considered the most prevalent posttranscriptional modification of mRNA. This study aimed to elucidate the effect of PRDX3 on liver fibrosis and the potential mechanism through which the m6A modification regulates PRDX3. PRDX3 expression was found to be negatively correlated with liver fibrosis in both animal models and clinical specimens from patients. We performed adeno-associated virus 9 (AAV9)-PRDX3 knockdown and AAV9-PRDX3 HSC-specific overexpression in mice to clarify the role of PRDX3 in liver fibrosis. PRDX3 silencing exacerbated hepatic fibrogenesis and hepatic stellate cell (HSC) activation, whereas HSC-specific PRDX3 overexpression attenuated liver fibrosis. Mechanistically, PRDX3 suppressed HSC activation at least partially via the mitochondrial reactive oxygen species (ROS)/TGF-β1/Smad2/3 pathway. Furthermore, PRDX3 mRNA was modified by m6A and interacted with the m6A readers YTH domain family proteins 1-3 (YTHDF1-3), as evidenced by RNA pull-down/mass spectrometry. More importantly, PRDX3 expression was suppressed when YTHDF3, but not YTHDF1/2, was knocked down. Moreover, PRDX3 translation was directly regulated by YTHDF3 in an m6A-dependent manner and thereby affected its function in liver fibrosis. Collectively, the results indicate that PRDX3 is a crucial regulator of liver fibrosis and that targeting the YTHDF3/PRDX3 axis in HSCs may be a promising therapeutic approach for liver fibrosis.
| S-EPMC9287738 | biostudies-literature
Project description:ObjectiveOur study aimed to evaluate the quality of radiomics studies on brain metastases based on the radiomics quality score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guidelines.Materials and methodsPubMed MEDLINE, and EMBASE were searched for articles on radiomics for evaluating brain metastases, published until February 2021. Of the 572 articles, 29 relevant original research articles were included and evaluated according to the RQS, TRIPOD checklist, and IBSI guidelines.ResultsExternal validation was performed in only three studies (10.3%). The median RQS was 3.0 (range, -6 to 12), with a low basic adherence rate of 50.0%. The adherence rate was low in comparison to the "gold standard" (10.3%), stating the potential clinical utility (10.3%), performing the cut-off analysis (3.4%), reporting calibration statistics (6.9%), and providing open science and data (3.4%). None of the studies involved test-retest or phantom studies, prospective studies, or cost-effectiveness analyses. The overall rate of adherence to the TRIPOD checklist was 60.3% and low for reporting title (3.4%), blind assessment of outcome (0%), description of the handling of missing data (0%), and presentation of the full prediction model (0%). The majority of studies lacked pre-processing steps, with bias-field correction, isovoxel resampling, skull stripping, and gray-level discretization performed in only six (20.7%), nine (31.0%), four (3.8%), and four (13.8%) studies, respectively.ConclusionThe overall scientific and reporting quality of radiomics studies on brain metastases published during the study period was insufficient. Radiomics studies should adhere to the RQS, TRIPOD, and IBSI guidelines to facilitate the translation of radiomics into the clinical field.
| S-EPMC8743155 | biostudies-literature
Project description:Metastatic progression remains a major burden for cancer patients and is associated with eventual resistance to prevailing therapies such as chemotherapy. Here, we reveal how chemotherapy induces extracellular matrix (ECM), wound healing and stem cell network in cancer cells via the c-Jun N-terminal kinase (JNK) pathway, leading to reduced therapeutic efficacy. We find that elevated JNK activity in cancer cells is linked to poor clinical outcome in breast cancer patients and is critical for tumor initiation and metastasis in xenograft mouse models of breast cancer. We show that JNK signaling enhances expression of the ECM and stem cell niche components osteopontin, also called secreted phosphoprotein 1 (SPP1), and tenascin C (TNC), that promote lung metastasis. We demonstrate that both SPP1 and TNC are direct targets of the c-Jun transcription factor. Exposure to multiple chemotherapies further exploits this JNK-mediated axis to confer treatment resistance. Importantly, JNK inhibition or disruption of SPP1 or TNC expression sensitizes experimental mammary tumors and metastases to chemotherapy, thus providing insights to consider for future treatment strategies against breast cancer.
| S-SCDT-EMM-2018-09003 | biostudies-other
Project description:Metastatic progression remains a major burden for cancer patients and is associated with eventual resistance to prevailing therapies such as chemotherapy. Here, we reveal how chemotherapy induces an extracellular matrix (ECM), wound healing, and stem cell network in cancer cells via the c-Jun N-terminal kinase (JNK) pathway, leading to reduced therapeutic efficacy. We find that elevated JNK activity in cancer cells is linked to poor clinical outcome in breast cancer patients and is critical for tumor initiation and metastasis in xenograft mouse models of breast cancer. We show that JNK signaling enhances expression of the ECM and stem cell niche components osteopontin, also called secreted phosphoprotein 1 (SPP1), and tenascin C (TNC), that promote lung metastasis. We demonstrate that both SPP1 and TNC are direct targets of the c-Jun transcription factor. Exposure to multiple chemotherapies further exploits this JNK-mediated axis to confer treatment resistance. Importantly, JNK inhibition or disruption of SPP1 or TNC expression sensitizes experimental mammary tumors and metastases to chemotherapy, thus providing insights to consider for future treatment strategies against metastatic breast cancer.
| S-EPMC6180299 | biostudies-literature