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Series GSE111363 Query DataSets for GSE111363
Status Public on Jan 14, 2019
Title Induction of DISE by tumor suppressive microRNAs
Organism Homo sapiens
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Many siRNAs and shRNAs induce a form of cell death in all cancer cells by silencing a set of critical survival genes in a process called death induced by survival gene elimination (DISE). Mechanistically, a 6mer seed sequence (position 2-7 of the guide strand) is sufficient to confer DISE-inducing activity. We have now performed a strand-specific screen testing the toxicity of all 4096 possible 6mer seed sequences in a neutral double-stranded siRNA backbone. We found an asymmetric preference for guanine in positions 1-3 and a G content of >80% of the 6mer seed in the most toxic siRNAs, which target survival genes that are GC rich in their 3'UTR. During over 800 million years of evolution, miRNAs have evolved to avoid guanine in their seed sequences. However, two tumor suppressive miRNAs were found to be killing cancer cells through DISE using G rich toxic 6mer seeds in cells exposed to genotoxic stress: 1) the p53 inducible miR-34 family; and 2) miR-320a, a noncanonical miRNA that is still expressed in cancer cells when miRNA processing genes are mutated. Our data suggest that most miRNAs have evolved to avoid induction of DISE but certain tumor suppressive miRNAs utilize this mechanism to kill cancer cells.
Overall design Pan Argonaute immunoprecipitation and small RNA cloning in HeyA8 and HCT116 wild-type and Drosha KO cells treated with doxorubicin
Contributor(s) Gao QQ, Putzbach WE, Murmann AE, Chen S, Sarshad AA, Ambrosini G, Bartom ET, Hafner M, Peter ME
Citation(s) 30374110
Submission date Mar 02, 2018
Last update date Jan 14, 2019
Contact name Markus Hafner
Phone 3014026956
Organization name NIH
Department NIAMS
Lab Markus Hafner
Street address 50 South Drive
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (16)
GSM3029217 HeyA8_Ctrl_1
GSM3029218 HeyA8_Ctrl_2
GSM3029219 HeyA8_20h_1
BioProject PRJNA436738
SRA SRP133850

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Supplementary file Size Download File type/resource
GSE111363_miRNAseq_in_HeyA8_and_HCT116.xlsx 4.1 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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