Friend or Foe? Primary Tumor represses distant metastases' growth via exosomal miRNA-1
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ABSTRACT:
PROVIDER: PRJNA883386 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21677766_1.fastq.gz | Fastqsanger.gz | |||
| SRR21677766_2.fastq.gz | Fastqsanger.gz | |||
| SRR21677767_1.fastq.gz | Fastqsanger.gz | |||
| SRR21677767_2.fastq.gz | Fastqsanger.gz | |||
| SRR21677768_1.fastq.gz | Fastqsanger.gz |
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Project description:Recently, exosome has been treated as a key mechanism for cell-to-cell communication. We thus demonstrated the roles of exosomes for the encoding messages between primary tumors and metastases. To investigate the difference between pTDE miRNA (primary tumor-derived exosomal miRNA) and mDE miRNA (metastases-derived exosomal miRNA), we isolated exosomal miRNA from each cell lines. Next, we performed small RNA sequencing for miRNA profiling. Compared with pTDE and mDE miRNAs, miR-1 is specifically abundunt in pTDE and also shows therapeutic effects to repress the growth of metastases after primary tumor resection.
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Project description:Results When compared with each other, primary tumors and regional metastases showed statistically indistinguishable gene expression patterns. Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast/mesenchymal genes, and by the high expression of a 13-gene profile (that is, the ‘vascular endothelial growth factor (VEGF) profile’) that included VEGF, ANGPTL4, ADM and the monocarboxylic acid transporter SLC16A3. At least 8 out of 13 of these genes contained HIF1α binding sites, many are known to be HIF1α-regulated, and expression of the VEGF profile correlated with HIF1α IHC positivity. The VEGF profile also showed prognostic significance on tests of sets of patients with breast and lung cancer and glioblastomas, and was an independent predictor of outcomes in primary breast cancers when tested in models that contained other prognostic gene expression profiles and clinical variables. Conclusions These data identify a compact in vivo hypoxia signature that tends to be present in distant metastasis samples, and which portends a poor outcome in multiple tumor types.
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