Coronin proteins are actin-related proteins containing WD repeat domains encoded by seven genes (CORO1A,CORO1B,CORO1C,CORO2A,CORO2B,CORO6, andCORO7) in the human genome. Analysis of large cohort data from The Cancer Genome Atlas revealed that expression ofCORO1A,CORO1B,CORO1C,CORO2A, andCORO7was significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues (p< 0.05). Moreover, high expression ofCORO1CandCORO2Asignificantly predicted the 5 year survival rate of patients with PDAC (p= 0.0071 andp= 0.0389, respectively). In this study, we focused onCORO1Cand investigated its functional significance and epigenetic regulation in PDAC cells. Knockdown assays using siRNAs targetingCORO1Cwere performed in PDAC cells. Aggressive cancer cell phenotypes, especially cancer cell migration and invasion, were inhibited byCORO1Cknockdown. The involvement of microRNAs (miRNAs) is a molecular mechanism underlying the aberrant expression of cancer-related genes in cancer cells. Ourin silicoanalysis revealed that five miRNAs (miR-26a-5p,miR-29c-3p,miR-130b-5p,miR-148a-5p, andmiR-217) are putative candidate miRNAs regulatingCORO1Cexpression in PDAC cells. Importantly, all five miRNAs exhibited tumor-suppressive functions and four miRNAs exceptmiR-130b-5pnegatively regulatedCORO1Cexpression in PDAC cells.CORO1Cand its downstream signaling molecules are potential therapeutic targets in PDAC.