2020
DOI: 10.1016/j.isci.2019.11.031
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6mer Seed Toxicity in Viral microRNAs

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Cited by 17 publications
(28 citation statements)
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“…The genes downregulated in the siGGGGGC transfected cells, were enriched in a reference set of recently defined survival genes (10) (Fig. 3A), similar to the activity we reported for the two tumor suppressive miRNAs miR-34a-5p and miR-15/16-3p and their matching 6mer seed containing siRNAs (12,14). A gene ontology analysis suggested that the form of cell death induced by siGGGGGC, siGGCAGU (the miR-34a-5p 6mer seed), and even the chemotherapeutic drug carboplatin were very similar with shared GO terms we had previously reported to characterize DISE (10,12,23).…”
Section: Sigggggc Is Highly Toxic To Multiple Cancer Cells and Prefersupporting
confidence: 82%
See 1 more Smart Citation
“…The genes downregulated in the siGGGGGC transfected cells, were enriched in a reference set of recently defined survival genes (10) (Fig. 3A), similar to the activity we reported for the two tumor suppressive miRNAs miR-34a-5p and miR-15/16-3p and their matching 6mer seed containing siRNAs (12,14). A gene ontology analysis suggested that the form of cell death induced by siGGGGGC, siGGCAGU (the miR-34a-5p 6mer seed), and even the chemotherapeutic drug carboplatin were very similar with shared GO terms we had previously reported to characterize DISE (10,12,23).…”
Section: Sigggggc Is Highly Toxic To Multiple Cancer Cells and Prefersupporting
confidence: 82%
“…This suggested that while in the context of si/shRNAs that are designed to selectively silence single genes DISE could be viewed as an off-target effect, in the context of the biological function of miRNAs, this activity should be considered an on-target activity. In agreement with this interpretation, are findings that established major tumor suppressive miRNA families such as miR-34/449-5p and miR-15/16-5p kill cancer cells largely through 6mer Seed Tox by targeting hundreds of survival genes (12,14,15). si/shRNAs with a toxic 6mer seed can be used to treat cancer in mice.…”
supporting
confidence: 56%
“…5E). In this analysis in which we applied a paired Student’s T test in three out of 4 patients, the most abundant upregulated miRNA was miR-15b-5p which can kill cancer cells in part through 6mer Seed Tox (27), and the most abundant downregulated nontoxic miRNA was again miR-125b-5p. Analysis of all patient tumor pairs suggests that the differences seen between primary tumors and matched recurrences in this rare patient population are due to intrinsic changes in the tumor cells.…”
Section: Resultsmentioning
confidence: 99%
“…In human cells, we recently identified the seed consensus GGGGGC (targeting the seed match GCCCCC in a miRNA like fashion) as the most toxic seed sequence across three cell lines (19). Toxic 6mer seeds are found in tumor-suppressive miRNAs, including the prototypical tumor suppressive miRNA families, miR-34/449-5p and miR-15/16-5p (21, 22), and we and others have shown that 6mer seed toxicity (6mer Seed Tox) can be developed for cancer treatment (17, 23). When we treated xenografted OC with siRNAs containing toxic seeds, normal tissues were unaffected (17).…”
Section: Introductionmentioning
confidence: 99%
“…The microRNA (miRNA) is non-coding single-stranded RNA molecules with the lengths of approximately 22 nucleotides and regulate gene expression at the posttranscriptional level [ [6] , [7] , [8] ]. The miRNA can regulate many types of cancers [ [9] , [10] , [11] , [12] ] and can be proto-oncogenes or tumour suppressor genes that are closely associated with many diseases [ 9 , 10 , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] ].…”
Section: Introductionmentioning
confidence: 99%