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Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

ABSTRACT: Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

PROVIDER: PRJNA941343 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23717235.fastq.gz	Fastqsanger.gz
	SRR23717236.fastq.gz	Fastqsanger.gz
	SRR23717237_1.fastq.gz	Fastqsanger.gz
	SRR23717237_2.fastq.gz	Fastqsanger.gz
	SRR23717238.fastq.gz	Fastqsanger.gz

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Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma.

Project description:The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.

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Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

Project description:Purpose: The goals of this study are to investigate the role of miRNAs in regulating pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) and PDAC progress. Methods: Total RNA-seq and miRNA-seq were performed on PDAC tumor and adjacent benigh tissues, and the miRNA profile was also investigated from the patient and healthy subject plasma. Single-cell RNA-seq was performed on one PDAC tissue, using 10x Genomics 5 prime gene expression technology. Results: The RNA-seq and miRNA-seq libraries were sequenced on Illumina NextSeq 550 or HiSeq 4000 (Illumina, San Diego, CA). All sequencing data were demultiplexed and converted into fastq files by Illumina bcl2fastq2 v2.17.14. Filtered sequence reads were mapped to reference genome GRCh38 using STAR (RNA-seq) or Botwie (miRNA-seq) with default settings. Single cell data was mapped and counted uisng Cellranger (v5.0). Conclusions: We identifed 322 and 49 differentially expressed miRNAs in PDAC tissue and patient plasma, respectively. We also identify 1,445 differentially expressed genes from PDAC tissue and paired the DEGs with their regualtory miRNAs through miRNA functional prediction.

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Gene expression in pancreatic ductal adenocarcinoma

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