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

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 both increases and decreases in the levels of specific miRNAs have been shown to promote tumor development, a global reduction in miRNAs is commonly observed in various human tumors. However, complete loss has not been documented, suggesting an essential function for miRNAs in tumorigenesis. Here we present the finding that transformed or immortalized Dicer-null somatic cells can be isolated readily in vitro, maintain the characteristics of Dicer-expressing controls and remain stably proliferative. Furthermore, Dicer-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. Overall design: Small RNAs from tumor cell lines (murine sarcoma KrasG12D, p53 -/-) with and without Dicer (Dicer f/-, Dicer -/-) were analyzed.

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Ravi A, Gurtan AM, Kumar MS, Bhutkar A, Chin C, Lu V, Lees JA, Jacks T, Sharp PA