ArticleBMC cancer2020
Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- Identification of circular RNAs in cardiac hypertrophy and cardiac fibrosis.Frontiers in pharmacology · 2022Article
- Identification ofFrontiers in cell and developmental biology · 2022Article
- Gene Coexpression Network Characterizing Microenvironmental Heterogeneity and Intercellular Communication in Pancreatic Ductal Adenocarcinoma: Implications of Prognostic Significance and Therapeutic Target.Frontiers in oncology · 2022Article
- Article
- miRNA‑7515 suppresses pancreatic cancer cell proliferation, migration and invasion via downregulating IGF‑1 expression.Oncology reports · 2021Article
- The correlation of the miR-29a/MMP9 axis withAmerican journal of translational research · 2021Article
- Unusual Case of Pancreatic Adenocarcinoma with Bladder Metastasis.Medicina (Kaunas, Lithuania) · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown to play a significant role in progression of PDAC. Earlier, we observed a PSC-specific downregulation of miR-29a in PDAC pancreas, however, the mechanism of action of the molecule in PSCs is still to be elucidated. The current study aims to clarify the regulation of miR-29a in PSCs and identifies functionally important downstream targets that contribute to tumorigenic activities during PDAC progression.
methodsIn this study, using RNAseq approach, we performed transcriptome analysis of paired miR-29a overexpressing and control human PSCs (hPSCs). Enrichment analysis was performed with the identified differentially expressed genes (DEGs). miR-29a targets in the dataset were identified, which were utilized to create network interactions. Western blots were performed with the top miR-29a candidate targets in hPSCs transfected with miR-29a mimic or scramble control.
resultsRNAseq analysis identified 202 differentially expressed genes, which included 19 downregulated direct miR-29a targets. Translational repression of eight key pro-tumorigenic and -fibrotic targets namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 and ADAMTS2 by miR-29a was observed in PSCs. Using pathway analysis, we find that miR-29a modulates effectors of IGF-1-p53 signaling in PSCs that may hinder carcinogenesis. We further observe a regulatory role of the molecule in pathways associated with PDAC ECM remodeling and tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions and collagen biosynthesis.
conclusionsTogether, our study presents a comprehensive understanding of miR-29a regulation of PSCs, and identifies essential pathways associated with PSC-mediated PDAC pathogenesis. The findings suggest an anti-tumorigenic role of miR-29a in the context of PSC-cancer cell crosstalk and advocates for the potential of the molecule in PDAC targeted therapies.
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