Dicer, Drosha, and Outcomes in Patients with Ovarian Cancer

• Published in: The New England journal of medicine Vol. 359; no. 25; pp. 2641 - 2650
• Main Authors: Merritt, William M, Lin, Yvonne G, Han, Liz Y, Kamat, Aparna A, Spannuth, Whitney A, Schmandt, Rosemarie, Urbauer, Diana, Pennacchio, Len A, Cheng, Jan-Fang, Nick, Alpa M, Deavers, Michael T, Mourad-Zeidan, Alexandra, Wang, Hua, Mueller, Peter, Lenburg, Marc E, Gray, Joe W, Mok, Samuel, Birrer, Michael J, Lopez-Berestein, Gabriel, Coleman, Robert L, Bar-Eli, Menashe, Sood, Anil K
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 18.12.2008
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cell Line, Tumor; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DNA Mutational Analysis; Endoribonucleases - genetics; Endoribonucleases - metabolism; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; General aspects; Gynecology. Andrology. Obstetrics; Humans; Kaplan-Meier Estimate; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medical sciences; MicroRNAs - metabolism; Middle Aged; Multivariate Analysis; Mutation, Missense; Neoplasm Staging; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - mortality; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - mortality; Prognosis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease III - genetics; Ribonuclease III - metabolism; RNA Interference; RNA, Messenger - metabolism; RNA, Small Interfering; Transfection; Treatment Outcome; Tumors; Human; Medicine; Ovarian diseases; Gene silencing; RNA interference; Prognosis; Ovary cancer; Evolution; Patient; Malignant tumor; Cancer; Female genital diseases
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0803785

Dicer and Drosha are RNase enzymes involved in RNA interference from precursor molecules. RNA interference can either silence or enhance the expression of specific target genes. This study of ovarian-cancer cells showed that the combination of low Dicer expression and low Drosha expression was associated with a poor prognosis and that low Dicer expression was an independent factor associated with a poor clinical outcome. Dicer and Drosha are RNase enzymes involved in RNA interference from precursor molecules. This study of ovarian-cancer cells showed that the combination of low Dicer expression and low Drosha expression was associated with a poor prognosis and that low Dicer expression was an independent factor associated with a poor clinical outcome. The discovery that gene expression can be altered through RNA interference 1 has stimulated research on the role of RNA interference in the development of cancer. Targeting specific genes by RNA-interference molecules allows for the identification of regulators of angiogenic, proliferative, and survival pathways in cancer cells. Furthermore, RNA-interference molecules that silence specific genes are being tested in preclinical studies as a treatment for cancer. 2 , 3 Regulation of gene expression through RNA interference occurs by means of microRNA (miRNA) or small interfering RNA (siRNA) (Figure 1). In the nucleus, endogenous double-stranded RNA segments are cut into short, hairpin-shaped double-stranded RNA precursor . . .