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

• Published in: Cancer cell Vol. 21; no. 6; pp. 848 - 855
• Main Authors: Ravi, Arvind, Gurtan, Allan M., Kumar, Madhu S., Bhutkar, Arjun, Chin, Christine, Lu, Victoria, Lees, Jacqueline A., Jacks, Tyler, Sharp, Phillip A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.06.2012
• Subjects: Animals; Antineoplastic Agents, Hormonal - pharmacology; Blotting, Northern; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cells, Cultured; DEAD-box RNA Helicases - deficiency; DEAD-box RNA Helicases - genetics; Flow Cytometry; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; MicroRNAs - genetics; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease III - deficiency; Ribonuclease III - genetics; Sarcoma - genetics; Sarcoma - metabolism; Sarcoma - pathology; Tamoxifen - pharmacology
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2012.04.037

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. ► ID1 and ID3 together govern the maintenance of colon cancer-initiating cells ► ID1 and ID3 orchestrate their effect through the cell cycle inhibitor, p21 ► ID1 and ID3 expression reduces sensitivity to the chemotherapeutic drug, oxaliplatin