MicroRNA molecules help cells control the amount and kinds of proteins they make, and abnormal levels of certain microRNAs are a hallmark of many cancers.
First author Flavia Pichiorri, assistant professor of hematology, notes that nucleolin is a promising therapeutic target for microRNA modulation in cancer cells.
- Nucleolin is present at abnormally high levels in breast cancer cells.
- AS1411 reduces nucleolin levels and inhibits the processing of certain cancer-associated microRNAs, including miR-21, miR-103, miR-221 and miR-222, whose overexpression in breast cancer is associated with drug resistance and aggressiveness.
- AS1411 affects breast-cancer-cell motility and invasiveness by reducing the expression of several genes targeted by nucleolin-related microRNAs (e.g., PTEN);
- Impairing nucleolin in fulvestrant-resistant breast-cancer cells restores sensitivity to the drug, suggesting that agents targeting nucleolin can improve the effectiveness of conventional anti-cancer agents.
Other researchers involved in this study were Dario Palmieri, Jessica Consiglio, Jia You, Tiffany Talabere, Alessandro Lagana, Jingwen Guan, Pierluigi Gasparini, Veronica Balatti, Vincenzo Coppola, Craig C. Hofmeister, Guido Marcucci, John C. Byrd, Stefano Volinia, Charles L. Shapiro and Michael A. Freitas, The Ohio State University; Luciana De Luca of IRCCS Centro di Riferimento Oncologico della Basilicata, Italy; Alberto Rocci, University of Turin, Italy; Claudia Piovan, Istituto Nazionale Tumori, Italy; and Luciano Cascione, University of Catania, Italy.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.