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

SummaryMicroRNAs 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.

► Sarcoma cells remain stably proliferative in the absence of DICER1 ► DICER1-null sarcoma cells form tumors in vivo, but with decreased kinetics ► Immortalized mesenchymal stem cells can similarly tolerate DICER1 loss ► MicroRNA levels in tumors may result from a complex stabilizing selection