Kwon, Jason J.Willy, Jeffrey A.Quirin, Kayla A.Wek, Ronald C.Korc, MurrayYin, Xiao-MingKota, Janaiah2017-08-012017-08-012016-11-01Kwon, J. J., Willy, J. A., Quirin, K. A., Wek, R. C., Korc, M., Yin, X.-M., & Kota, J. (2016). Novel role of miR-29a in pancreatic cancer autophagy and its therapeutic potential. Oncotarget, 7(44), 71635–71650. http://doi.org/10.18632/oncotarget.11928https://hdl.handle.net/1805/13692Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy that responds poorly to current therapeutic modalities. In an effort to develop novel therapeutic strategies, we found downregulation of miR-29 in pancreatic cancer cells, and overexpression of miR-29a sensitized chemotherapeutic resistant pancreatic cancer cells to gemcitabine, reduced cancer cell viability, and increased cytotoxicity. Furthermore, miR-29a blocked autophagy flux, as evidenced by an accumulation of autophagosomes and autophagy markers, LC3B and p62, and a decrease in autophagosome-lysosome fusion. In addition, miR-29a decreased the expression of autophagy proteins, TFEB and ATG9A, which are critical for lysosomal function and autophagosome trafficking respectively. Knockdown of TFEB or ATG9A inhibited autophagy similar to miR-29a overexpression. Finally, miR-29a reduced cancer cell migration, invasion, and anchorage independent growth. Collectively, our findings indicate that miR-29a functions as a potent autophagy inhibitor, sensitizes cancer cells to gemcitabine, and decreases their invasive potential. Our data provides evidence for the use of miR-29a as a novel therapeutic agent to target PDAC.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesPancreatic cancerAutophagyGemcitabineMetastasismiR-29Article