Proliferation and tumorigenesis of a murine sarcoma cell line in the absence of DICER1.
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.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Arvind
A
Ravi
Allan M
AM
Gurtan
Madhu S
MS
Kumar
Arjun
A
Bhutkar
Christine
C
Chin
Victoria
V
Lu
Jacqueline A
JA
Lees
Tyler
T
Jacks
Phillip A
PA
Sharp
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D035683:MicroRNAs; D013629:Tamoxifen; D049452:Green Fluorescent Proteins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases