Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE75428 | GEO | 2015/11/27
SECONDARY ACCESSION(S): PRJNA304246
REPOSITORIES: GEO
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Project description:To investigate the function of Neuropilin-1 (NRP-1) in breast cancer MDA-MB-231 cells. CRISPR-Cas9 gene editing was used to knockout (KO) the NRP-1 gene in MDA-MB-231 human triple-negative breast cancer cells. Differentially expressed genes (DEGs) were determined in NRP-1 KO and parental MDA-MB-231 cells using whole transcriptome next-generation sequencing.
2023-04-11 | GSE229031 | GEO
Project description:Background: Neuropilin-1 (NRP-1) is a non-tyrosine kinase glycoprotein receptor that elicits multiple functions depending on the ligand bound. It is known to promote cancer progression however; transcriptome-wide changes triggered by NRP-1 are not defined. In this study we aimed to identify novel molecules associated with NRP-1 expression using a global transcriptomic approach in a recombinant breast cancer cell model. Methods: NRP-1 was stably overexpressed in the BT-474 breast cancer cell line (BT-474 NRP-1) and subjected to next generation RNA sequencing using the Illumina HiSeq 4000 sequencing system. Two replicates each of the control BT-474 and BT474-NRP1 were utilized for sequencing. The count per million (CPM) method was utilized for filtering low counts/noise by NOISeq. The clean reads were mapped to reference genome using HISAT/ Bowtie2 tool. The Fragments Per Kilobase of transcript per Million mapped reads (FPKM) method was utilized to calculate the expression levels. False Detection Rate (FDR) ≤ 0.001, absolute value of Log2 ratio ≥ 2 and consistency between the two replicates were used as the default threshold to identify significant DEGs. Results: A total of 22,655,647 clean reads from 22,914,684 raw sequencing reads were generated upon sequencing. 22 upregulated and 61 downregulated genes were identified. Among the DEGs, 11 upregulated and 11 downregulated genes were shortlisted based on their known roles in cancer and/or EMT for confirmation with real-time qPCR. 2 upregulated genes TNC and TARP and 5 downregulated genes ACE, APOD, DDIT3, P2RX6 and ATF3 indicated consistently differential expression with qPCR. Conclusion: We report for the first time the global transcriptome-wide changes elicited by NRP-1 overexpression in a breast cancer cell model. Our study identified the novel association between several candidate molecules such as TNC, a known oncogene, and NRP-1 expression that may controbute to the tumourigenic role of NRP-1 in breast cancer.
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Project description:Objective: Trastuzumab has been used for the treatment of HER2-positive breast cancer (BC). However, a subset of BC patients exhibited resistance to trastuzumab therapy. Thus, clarifying the molecular mechanism of trastuzumab treatment will be beneficial to improve the treatment of HER2-positive BC patients. In this study, we identified trastuzumab-responsive microRNAs that are involved in the therapeutic effects of trastuzumab. Methods and results: RNA samples were obtained from HER2-positive (SKBR3 and BT474) and HER2-negetive (MCF7 and MDA-MB-231) cells with and without trastuzumab treatment for 6 days. Next, we conducted a microRNA profiling analysis using these samples to screen those microRNAs that were up- or downregulated only in HER2-positive cells. This analysis identified miR-26a and miR-30b as trastuzumab-inducible microRNAs. Transfecting miR-26a and miR-30b induced cell growth suppression in the BC cells by 40% and 32%, respectively. A cell cycle analysis showed that these microRNAs induced G1 arrest in HER2-positive BC cells as trastuzumab did. An Annexin-V assay revealed that miR-26a but not miR-30b induced apoptosis in HER2-positive BC cells. Using the prediction algorithms for microRNA targets, we identified cyclin E2 (CCNE2) as a target gene of miR-30b. A luciferase-based reporter assay demonstrated that miR-30b post-transcriptionally reduced 27% (p=0.005) of the gene expression by interacting with two binding sites in the 3’-UTR of CCNE2. Conclusion: In BC cells, trastuzumab modulated the expression of a subset of microRNAs, including miR-26a and miR-30b. The upregulation of miR-30b by trastuzumab may play a biological role in trastuzumab-induced cell growth inhibition by targeting CCNE2. We obtained microRNA expression profiles of breast cancer cell lines, MCF7, MDA-MB-231, SKBR3, and BT474, with or without trastuzumab (4microgram/mL) treatment.
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2012-06-03 | GSE38415 | GEO
Project description:The HER2 overexpressing and the Triple Negative Breast Cancer forms (TNBC) remain the most aggressive subtypes of BC with poor prognosis, frequent disease relapse and metastasis. In this study the aim was to identify key membrane-associated proteins which are overexpressed in these aggressive BC subtypes and can serve as potential biomarkers or drug targets. We leveraged on the development of a membrane enrichment protocol in combination with the global profiling GeLC-MS/MS technique, and compared the proteomic profiles of a HER2 overexpressing (HCC-1954) and a TNBC (MDA-MB-231) cell line with that of a benign control breast cell line (MCF-10A). An average of 2300 proteins were identified from each cell line, of which approximately 600 were membrane-associated proteins. Our global proteomic methodology in tandem with invigoration by Western blot and Immunofluorescence analysis, readily detected several previously-established BC receptors like HER2 and EPHA2, but importantly STEAP4 and CD97 emerged as novel potential candidate markers.
2023-03-10 | PXD021819 | Pride
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