Luteolin-regulated MicroRNA-301-3p Targets Caspase-8 and Modulates TRAIL Sensitivity in PANC-1 Cells

• Published in: Anticancer research Vol. 40; no. 2; pp. 723 - 731
• Main Authors: Moeng, Sokviseth, Son, Seung Wan, Seo, Hyun Ah, Lee, Jong Sun, Kim, Chung Kwon, Kuh, Hyo Jeong, Park, Jong Kook
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.02.2020
• Subjects: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Cancer; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Caspase 8 - genetics; Caspase 8 - metabolism; Caspase-8; Cell growth; Cell Line, Tumor; Cell proliferation; Cytotoxicity; Down-Regulation - drug effects; Drug Synergism; Gene expression; Gene Knockdown Techniques; Humans; Luteolin - administration & dosage; Luteolin - pharmacology; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Recombinant Proteins - pharmacology; Ribonucleic acid; RNA; TNF-Related Apoptosis-Inducing Ligand - administration & dosage; TNF-Related Apoptosis-Inducing Ligand - pharmacology; Toxicity; Transfection; luteolin; combination effect; caspase-8; miRNA-301-3p; pancreatic cancer; TRAIL
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14003

MicroRNAs (miRNAs) play regulatory roles in pancreatic ductal adenocarcinoma (PDAC). However, it is still required to identify the function of miRNA-301-3p in pancreatic cancer cells. Effects of luteolin on cell growth, TRAIL cytotoxicity, and miR-301-3p levels were evaluated. The role of miRNA-301-3p in regulating cell proliferation, target gene expression, and TRAIL cytotoxicity were studied. The levels of miR-301-3p were down-regulated in PANC-1 cells exposed to luteolin, which inhibits the growth of PANC-1 cells and sensitizes cells to TRAIL. The knockdown of miR-301-3p attenuates cell proliferation and enhances TRAIL cytotoxicity. In addition, caspase-8 was directly targeted by miR-301-3p. Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.