OBJECTIVES: This study aimed to identify microRNAs as novel biomarkers for improved diagnosis, prognosis prediction, and as a therapeutic target for pancreatic cancer. microRNAs may have a general role by acting as superordinated key regulators of tumorigenesis. METHODS: Individual cellular molecules of multiple pathways associated with pancreatic cancer were analyzed for common microRNA binding sites, thereby enabling the identification of key regulating microRNAs. The potential of the identified microRNAs was subsequently determined in cell culture experiments. RESULTS: Using bioinformatic pathway analyses, miR-548d was identified to target multiple components of pancreatic cancer-related pathways. The effect of microRNA on pancreatic cells was determined by overexpression studies using PANC-1 cells, resulting in impaired cell proliferation because of increased apoptosis and cell cycle arrest. In addition, miR-548d overexpression led to a sensitization to gemcitabine. CONCLUSIONS: MicroRNA miR-548d was identified as a potential superior regulator for the development and progression of pancreatic cancer by targeting multiple factors of crucial pathways. Therapeutically, microRNAs with superordinate function, such as miR-548d, may be promising diagnostic and therapeutic tools for the future treatment of pancreatic cancer.
OBJECTIVES: This study aimed to identify microRNAs as novel biomarkers for improved diagnosis, prognosis prediction, and as a therapeutic target for pancreatic cancer. microRNAs may have a general role by acting as superordinated key regulators of tumorigenesis. METHODS: Individual cellular molecules of multiple pathways associated with pancreatic cancer were analyzed for common microRNA binding sites, thereby enabling the identification of key regulating microRNAs. The potential of the identified microRNAs was subsequently determined in cell culture experiments. RESULTS: Using bioinformatic pathway analyses, miR-548d was identified to target multiple components of pancreatic cancer-related pathways. The effect of microRNA on pancreatic cells was determined by overexpression studies using PANC-1 cells, resulting in impaired cell proliferation because of increased apoptosis and cell cycle arrest. In addition, miR-548d overexpression led to a sensitization to gemcitabine. CONCLUSIONS: MicroRNA miR-548d was identified as a potential superior regulator for the development and progression of pancreatic cancer by targeting multiple factors of crucial pathways. Therapeutically, microRNAs with superordinate function, such as miR-548d, may be promising diagnostic and therapeutic tools for the future treatment of pancreatic cancer.
Authors: Tint Lwin; Xiaohong Zhao; Fengdong Cheng; Xinwei Zhang; Andy Huang; Bijal Shah; Yizhuo Zhang; Lynn C Moscinski; Yong Sung Choi; Alan P Kozikowski; James E Bradner; William S Dalton; Eduardo Sotomayor; Jianguo Tao Journal: J Clin Invest Date: 2013-11 Impact factor: 14.808
Authors: Jack W Rostas; Hawley C Pruitt; Brandon J Metge; Aparna Mitra; Sarah K Bailey; Sejong Bae; Karan P Singh; Daniel J Devine; Donna L Dyess; William O Richards; J Allan Tucker; Lalita A Shevde; Rajeev S Samant Journal: Mol Cancer Date: 2014-08-29 Impact factor: 27.401