Explorative Role of miR-216a/217 as a Tumor Suppressor in Pancreatic Cancer

Pancreatic cancer (PC) is a lethal malignancy with a 5-year survival rate of 10.8%. Gemcitabine, in combination with Abraxane and Folfirinox, are current treatments available for metastatic PC, however, all these therapies provided limited patient survival benefit, often resulting in high toxicity. Therefore, there is a need to identify novel therapeutic targets and combination therapies to combat this lethal cancer. MicroRNAs (miRNAs or miRs) have been shown to regulate PC proliferation and metastasis. Recently, miRNA therapies have shown promising results as a single miRNA is predicted to target more than 200 genes, involved in multiple pathways. The objective of this study is to understand the role of miR-216a/217 in PC growth and its progression. We and others have shown that miR-216a/217 was progressively downregulated during PC progression. PC patients with higher miR-216a/217 had better survival. Our In-situ hybridization data showed reduced expression of miR-216a/217 in PC patient samples (TMA - 196 core). Further, over-expression of miR-216a/217 in Capan-1 PC cells in vitro resulted in inhibition of cell proliferation and the epithelial-mesenchymal transition (EMT). In silico analysis have identified protein tyrosine phosphatase type IVA member 1 (PTP4A1) as a direct downstream target of miR-216a/217 in PC. Furthermore, our data indicates that miR-216a/217 inhibits PC metastasis by targeting PTP4A1 and may serve as a prospective therapeutic target in PC.https://digitalcommons.unmc.edu/surp2022/1022/thumbnail.jp