Abstract 2790: Identification of tumor suppressor miRNA to regulate FXYD3 in pancreatic cancer cells

Abstract Pancreatic cancer (PC) continues to be one of the deadliest cancers globally, ranking among the top causes of cancer-related mortality. Despite significant progress in medical research, effective methods for early diagnosis and treatment remain challenging, contributing to poor survival rates. MicroRNAs (miRNAs), small non-coding RNA molecules that consist of 18-25 nucleotides, have emerged as critical regulators of gene expression as therapeutic agents and diagnostic biomarkers. Recently, the oncogene FXYD3 has gained attention as a candidate for early detection, offering a promising result for research. In this study, we applied bioinformatic analyses to identify potential interactions between tumor-suppressing miRNAs and the oncogene FXYD3. Our findings revealed that several miRNAs directly target FXYD3, highlighting their role in regulating its expression. To validate these predictions, we performed immunohistochemistry (IHC) analysis. The results confirmed that these miRNAs were significantly overexpressed in normal pancreatic tissues compared to PC tissues. These observations suggested that the loss of specific miRNAs could contribute to the upregulation of FXYD3, promoting tumor progression. Interestingly, our study also found differential expression patterns of these miRNAs across various pancreatic cancer cell lines, indicating cell-type-specific regulatory mechanisms. The findings of the functional assays using miRNA mimics or inhibitors provide a foundation for developing miRNA-based therapeutic strategies targeting FXYD3. In summary, this study emphasizes the importance of miRNAs that target FXYD3 in pancreatic cancer. Our research supports their role as tumor suppressors and underscores their therapeutic potential in combating one of the most aggressive and challenging cancers. Citation Format: Alejandra Ke Xin Yee, Kuen-Haur Lee. Identification of tumor suppressor miRNA to regulate FXYD3 in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2790.