V39: Differentially Expressed Micrornas from Cancer-associated Fibroblasts Display Tumor-suppressive Behaviors in Pancreatic Cancer

Wednesday, March 2, 2022

6:07 PM – 6:10 PM CST

Location: Zoom Meeting

Virtual Poster Presenter(s)

Gerik W. Tushoski-Alemán, B.S. B.M.

Clinical Research Coordinator
University of Florida
Gainesville, Florida, United States

Disclosure: Disclosure information not submitted.

Participants should be aware of the following financial/non-financial relationships:

Gerik W. Tushoski-Alemán, B.S. B.M.: Disclosure information not submitted.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplasia that consists largely of cancer-associated fibroblasts (CAFs). Prior studies suggested that CAFs confer resistance to conventional therapeutics. However, subsequent CAF depletion strategies paradoxically facilitated tumor progression. We recently discovered and reported that CAF and PDAC cells effectively exchange exosomes enriched with microRNAs (miRNA). We hypothesized that these microRNAs are functionally tumor suppressive.

Methods: We identified differentially expressed miRNAs in CAF cells (compared to PDAC cells) using NanoString miRNA assays. Cell proliferation, viability, migration, and invasion assays were performed on cells transfected with the two most differentially expressed miRNAs. The functions of additional, differentially expressed miRNAs of interest were explored in PubMed.gov using the keywords miR- “X” and cancer. Article conclusions were sorted into tumor-suppressive or oncogenic categories. Ingenuity Pathway Analysis (IPA) was used to identify target genes of these microRNAs and predict functional impact.

Results: Transfection into PDAC cells of the two most differentially expressed CAF miRNAs (miR-145-5p and miR-199a-5p) decreased cell viability, proliferation, migration, and invasion in vitro, and pooled transfection delivered greater impact to these properties. Through a comprehensive literature analysis, we discovered that 94.52% (921/974) of articles described these microRNAs as tumor-suppressive. Among 15 miRNAs evaluated, 8 had their function evaluated in pancreatic cancer. All of these 8 microRNAs were documented as tumor-suppressive, with none reporting an oncogenic function. IPA identified 47 target genes in PDAC signaling pathways, including 5 genes with prognostic significance. The putative target genes of these microRNA are strongly associated with the cellular development, growth, proliferation, and migration of cells.

Conclusions:

Taken together, our work suggests that differentially expressed microRNAs produced by CAFs predominantly induce tumor-suppressive biological functions in PDAC.

Learning Objectives:

Upon completion, participants will be able to better understand the role of differentially expressed microRNA from cancer-associated fibroblasts in the context of the pancreatic cancer tumor microenvironment.
Upon completion, participants will be able to describe what makes a microRNA tumor-suppressive or oncogenic.
Upon completion, participants will be able to recall how transfection of miR-145-5p and miR-199a-5p affected pancreatic cancer cell viability and proliferation.