# The initiation of exosome microRNA signaling in pancreatic cancer cells

> **NIH NIH R03** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $72,500

## Abstract

Project Summary
 The high mortality rate of pancreatic ductal adenocarcinoma (PDAC) is primarily attributed to its
aggressive nature for which the underlying biology remains elusive. Exosome microRNA (miRNA)-mediated
intercellular communication is a critical signaling event in the tumor microenvironment that drives PDAC
progression. While recent studies have shown that cancer exosomes selectively encapsulate certain miRNA
species and deliver them to surrounding cells, very little is known about how exosome miRNA signaling is
initiated in cancer cells and processed in the tumor microenvironment to promote tumor progression. In our
preliminary studies we have observed that a group of miRNAs is selectively encapsulated and highly
enriched in exosomes derived from PDAC cells, with miR-1246 being the highest enriched. Bioinformatics
analysis revealed three miRNA motifs that are present in the miR-1246 sequence and commonly shared by
the highly enriched exosome miRNAs. Further, using a biotin-labeled miR-1246 probe and proteomic
analysis, we have identified SRSF1, TIA1, and EIF3B as the most abundant cellular proteins specifically
associated with miR-1246. Based on these observations we hypothesize that RBPs interact with miRNA
sequence motifs to control the selective encapsulation and enrichment of exosome miRNAs in
PDAC cells, thereby initiating exosome miRNA signaling that promotes PDAC progression. We
propose three specific aims to test this hypothesis. Specific Aim 1, To identify the miRNA sequence
motifs that mediate exosome miRNA encapsulation in PDAC cells; Specific Aim 2, to determine
whether SRSF1, TIA1, and EIF3B regulate selective exosome miRNA encapsulation in PDAC cells;
Specific Aim 3, to examine whether exosome miR-1246 promotes PDAC progression in vivo. Upon
completion of the proposed studies, we anticipate that we will have identified RBPs and miRNA motifs that
mediate selective exosome miRNA encapsulation in PDAC cells, and determined the role of exosome miR-
1246 in promoting PDAC progression. A better understanding of how exosome miRNA signaling is initiated
and processed will help establish new therapeutic strategies against PDAC.

## Key facts

- **NIH application ID:** 9848512
- **Project number:** 5R03CA235208-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Wei-Qun Ding
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $72,500
- **Award type:** 5
- **Project period:** 2019-01-09 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848512

## Citation

> US National Institutes of Health, RePORTER application 9848512, The initiation of exosome microRNA signaling in pancreatic cancer cells (5R03CA235208-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9848512. Licensed CC0.

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