Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE102155
PROVIDER: PRJNA396880 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that is difficult to treat as it is unresponsive to hormone-therapy; therefore, it is imperative to identify novel, targetable regulators of progression in TNBC. Long non-coding RNAs (lncRNAs) are important regulators in breast cancer and have great potential as therapeutic targets; however, little is known about how the majority of lncRNAs function within TNBC cells. In this study, we identify a novel lncRNA, MANCR (LINC00704), which is upregulated in TNBC cells and breast cancer patient samples. Depletion of MANCR in TNBC cells results in a significant decrease in cell proliferation and viability with a concomitant increase in DNA damage. Transcriptome-wide sequencing following MANCR knockdown reveals significant differences in the expression of >2000 genes, and gene set enrichment analysis identifies changes in multiple categories related to cell cycle regulation. Furthermore, MANCR expression is highest in mitotic cells by both RT-qPCR and RNA in situ hybridization. Consistent with a possible role in cell cycle regulation, MANCR-depleted cells have a lower mitotic index and a higher incidence of defective cytokinesis. Taken together, our data reveal a role for the novel lncRNA, MANCR (mitotically-associated long non-coding RNA), in cell cycle regulation of aggressive breast cancer, and identify it as a potential therapeutic target.
2018-01-31 | GSE102155 | GEO
Project description:Identifying long non-coding RNAs in triple-negative breast cancer
| PRJNA271881 | ENA
Project description:Long non-coding RNA landscape of patients biopsies from advanced Triple Negative Breast Cancer
| PRJNA734951 | ENA
Project description:ADAR1 catalyzes Adenosine-to-Inosine (A-to-I) editing of double-stranded RNA and regulates global expression output through its interactions with RNA and other proteins. ADARs play important roles in development and disease, and previous work has shown that ADAR1 is oncogenic in a growing list of cancer types. Here we show that ADAR1 is important for growth and invasion in triple negative breast cancer cells, as ADAR1 loss yields reduced growth, migration & invasion, and mammosphere formation. Global RNA-seq analyses demonstrate that ADAR1 regulates both coding and non-coding targets via expression level and/or A-to-I editing. We demonstrated that a recoding edit in FLNB (chr3:58156064) inhibits the tumor suppressive activities of the protein to promote growth & invasion. We show that several tumor suppressor microRNAs are also downregulated by ADAR1 to promote cell cycle progression and invasion. This work describes several novel mechanisms of ADAR1-mediated oncogenesis in triple negative breast cancer, providing support to strategies for targeting ADAR1 in this aggressive cancer type with few treatment options.
2022-03-14 | GSE177056 | GEO
Project description:Long non-coding RNAs (lncRNAs) represent a novel class of anti-cancer therapeutic targets. Hypoxia-induced lncRNAs are associated with the aggressive tumor phenotypes and might serve as putative drug targets. Here, we unraveled lncRNAs whose expression is upregulated in hypoxic breast tumors. One of the hypoxia-induced lncRNA, LAS3 (LncRNA Associated to SART3), is commonly upregulated not only in all breast cancer subtypes, but also in several types of epithelial cancers. LAS3 expression is driven by the stress-induced JNK/c-JUN pathway, which is frequently activated in human cancer. By pull down of LAS3 coupled to mass spectrometry-based proteomics, we identified SART3, a component of the splicing machinery, as a LAS3-interacting partner. In a second proteomics experiment, pull down of SART3-containing complexes from MCF10A cells treated with either scramble, or LAS3-specific GapmeRs showed that LAS3 regulates splicing efficiency by triggering SART3 dissociation from the U4/U6 snRNP during the recycling phase of the spliceosome cycle. Finally, differential shotgun analysis of MDA-MB-231/tet-shLAS3 cells allowed us to quantify expression of 2,940 proteins. Here, genes with significant intron retention showed decreased protein expression levels, indicating that widespread LAS3-mediated intron retention disrupts open reading frame integrity leading to stochastic decrease of protein expression and decreased fitness of cancer cells. Together, our data show that LAS3 is essential for growth of LAS3-positive triple negative breast tumors and indicate that LAS3 inhibition might be a suitable therapeutic approach for breast cancer treatment.
2020-05-26 | PXD013334 | Pride
Project description:NEK2 regulates triple negative breast cancer transcriptome.
| PRJNA590988 | ENA
Project description:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of ï?¢-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer. 14 pretreatment non-triple negative breast tumors compare with 5 triple negative breast tumor.
2011-06-01 | E-GEOD-27447 | biostudies-arrayexpress
Project description:Protein hydroxylation extensively regulates cellular signaling by affecting protein stability, protein-protein interaction and protein activity, and its dysregulation contributes to the pathogenesis of various diseases including cancers. However, because of the transient nature of the enzyme-substrate interaction, identifying new prolyl hydroxylation substrates remains a daunting challenge. Here, by developing a novel substrate-trapping strategy combining tumor hypoxia and hydroxylase pharmacological inhibition with TAP-TAG purification followed by mass spectrometry, we identify ADSL as a bona fide EglN2 prolyl hydroxylase substrate in triple negative breast cancer (TNBC). ADSL expression is significantly higher in TNBC than in the other breast cancer subtypes and normal breast tissues. Functionally, ADSL knock out greatly impairs TNBC 2-D and 3-D cell proliferation and invasiveness in vitro, as well as TNBC tumorigenesis and metastasis in xenograft models. Mechanistically, the integrated transcriptome and metabolome analysis reveals that ADSL promotes the activation of the oncogene cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL hydroxylation. Specifically, ADSL, by affecting adenosine levels, controls the expression of the long non-coding RNA MIR22HG, which negatively regulates the oncogene cMYC protein level and, thus, cMYC target gene expression. Our findings identify ADSL and ADSL hydroxylation as potential therapeutic targets in TNBC.
2020-10-06 | PXD015773 | Pride
Project description:The development of triple-negative breast cancers (TNBCs) – a subset of tumors with particularly aggressive pathogenesis – is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating a multitude of signaling nodes that propagate malignant traits in neighboring cancer cells. Characterization of these signaling cascades will better our understanding of TNBC biology, and stands to bring about novel therapeutics that can eliminate the morbidity and mortality associated with advanced disease. Here, we particularly focused on an emerging family of non-coding RNAs – called long non-coding RNAs or lncRNAs – and utilized a MSC-supported TNBC progression model to identify specific lncRNAs of functional relevance to TNBC pathogenesis. We used Affymetrix arrays to identify the gene expression changes that breast cancer cells (in this case, MDA-MB-231 cells) exhibit as they interact with admixed human MSCs
2021-06-09 | GSE171121 | GEO
Project description:Novel long non‐coding RNA 005620 induces epirubicin resistance of triple-negative breast cancer via regulating ITGB1 expression
| PRJNA638080 | ENA