Proliferation and Tumorigenesis of a Murine Sarcoma Cell Line in the Absence of DICER1

• DOI: 10.1016/j.ccr.2012.04.037
• Publication Date: 2012-06-11T18:16:24Z
• Authors: Arvind Ravi; Allan M. Gurtan; Madhu S. Kumar; Arjun Bhutkar; Christine Chin; Victoria Lu; Jacqueline A. Lees; Tyler Jacks; Phillip A. Sharp
• Keywords: 0301 basic medicine; Cancer Research; Antineoplastic Agents, Hormonal; Blotting, Western; Green Fluorescent Proteins; Mice, Transgenic; DEAD-box RNA Helicases; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Cells, Cultured; Cell Proliferation; Mice, Knockout; Gene Expression Profiling; Mesenchymal Stem Cells; Cell Biology; Blotting, Northern; Flow Cytometry; 3. Good health; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; MicroRNAs; Cell Transformation, Neoplastic; Oncology

MicroRNAs are a class of short ~22 nucleotide RNAs predicted to regulate nearly half of all protein coding genes, including many involved in basal cellular processes and organismal development. Although a global reduction in miRNAs is commonly observed in various human tumors, complete loss has not been documented, suggesting an essential function for miRNAs in tumorigenesis. Here we present the finding that transformed or immortalized Dicer1 null somatic cells can be isolated readily in vitro, maintain the characteristics of DICER1-expressing controls and remain stably proliferative. Furthermore, Dicer1 null cells from a sarcoma cell line, though depleted of miRNAs, are competent for tumor formation. Hence, miRNA levels in cancer may be maintained in vivo by a complex stabilizing selection in the intratumoral environment.