Biological functions of microRNA-216 and microRNA-217 during the development of pancreatic cancer
Year: 2013
Type: article
Abstract: Pancreatic cancer is among the most lethal of all human diseases.With a 5-year survival of less than 6%, there is a dire need for new therapeutic options [1].Molecular understanding of the disease is vital to overcome barriers to effective treatment.Here we evaluate the expression of noncoding RNAs in patient tissues, cell lines, in vitro model systems and in a genetically engineered mouse model that recapitulates the disease progression in humans.Two different classes of noncoding RNAs were studied, microRNA (miRNA) and transcribed ultraconserved elements (T-UCRs).Corroborating previously published data, we identify a miRNA cluster (miR-216a, miR-216b, and miR-217) that is consistently down-regulated in the different models of the disease.These miRNAs, are pancreas enriched, and appear to be acinar cell specific.A large percentage of the 482 known T-UCRs had increased expression in pancreatic cancer tissues, cell lines and in an in vitro system that mimics the pancreatic desmoplastic reaction.We hypothesized that loss of miR-216/-217 expression might be a crucial step in regulating acinar-to-ductal metaplasia (ADM).Although historically believed to originate in the ductal cells, compounding evidence now has shifted the paradigm to an acinar cell origin of the malignancy.miR-216/-217 expression decreases using an in vitro model that mimics the ADM process.Adenovirus overexpression of miR-217 during the in vitro have developed as a person and as scientist because of this, but the process was not easy.Dr. Schmittgen's confidence in my abilities is the reason why I am able to write this dissertation today.Thank you for entrusting me with such an important question and allowing me to grow scientifically in my own way.Second, I would like to thank all my lab mates, past and present, for the personal help, friendship and countless shared hours in the lab.I would specially like to thank Jong-Kook Park, Dhruvit Sutaria and JinMai Jiang for the special support they have provided.Jong-Kook for all the late nigh scientific
Author: Ana Clara P. Azevedo‐Pouly
Institution: The Ohio State University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2613730752