Data from Reduced DICER1 Elicits an Interferon Response in Endometrial Cancer Cells Article Swipe
Katherine B. Chiappinelli
,
Brian C. Haynes
,
Michael R. Brent
,
Paul J. Goodfellow
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1541-7786.c.6541780.v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1541-7786.c.6541780.v1
DICER1 is essential for the generation of mature miRNAs and other short noncoding RNAs. Several lines of investigation implicate DICER1 as a tumor suppressor. Reduced DICER1 levels and changes in miRNA abundance have been associated with aggressive tumor phenotypes. The global effects of reduced DICER1 on mRNA transcript abundance in tumor cells remain largely unknown. We used short hairpin RNA to stably knock down DICER1 in endometrial cancer cell lines to begin to determine how reduced DICER1 activity contributes to tumor phenotypes. DICER1 knockdown did not affect cell proliferation but caused enhanced cell migration and growth in soft agar. miRNA and mRNA profiling in KLE cells revealed overall decreases in miRNA levels and changes in the relative abundance of many mRNAs. One of the most striking changes in mRNA levels was the upregulation of IFN-stimulated genes (ISG), the majority of which lack known miRNA target sequences. IFNβ, a key upstream regulator of the IFN response, was significantly increased in DICER1 knockdowns in the AN3CA, Ishikawa, and KLE endometrial cancer cell lines and in the normal endometrial cell line EM-E6/E7/TERT. IFNβ secreted in media from KLE and EM-E6/E7/TERT shDcr cells was sufficient to activate an IFN response in HT29 cells. The reduced miRNA processing in DICER1 knockdowns was associated with increases in pre-miRNAs in the cytoplasm. Our findings suggest that elevated pre-miRNA levels trigger the IFN response to double-stranded RNA. We thus report a novel effect of reduced DICER1 function in cancer cells. Mol Cancer Res; 10(3); 316–25. ©2012 AACR.
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- preprint
- Language
- en
- Landing Page
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- References
- 40
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https://doi.org/10.1158/1541-7786.c.6541780.v1Digital Object Identifier
- Title
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Data from Reduced DICER1 Elicits an Interferon Response in Endometrial Cancer CellsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-04-03Full publication date if available
- Authors
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Katherine B. Chiappinelli, Brian C. Haynes, Michael R. Brent, Paul J. GoodfellowList of authors in order
- Landing page
-
https://doi.org/10.1158/1541-7786.c.6541780.v1Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1158/1541-7786.c.6541780.v1Direct OA link when available
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Gene knockdown, microRNA, Downregulation and upregulation, Biology, Cancer research, Cell culture, Cell growth, Endometrial cancer, Phenotype, Gene silencing, Messenger RNA, Cell, Gene, Cell biology, Cancer, GeneticsTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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| abstract_inverted_index.mRNA | 46, 101, 128 |
| abstract_inverted_index.many | 119 |
| abstract_inverted_index.most | 124 |
| abstract_inverted_index.soft | 97 |
| abstract_inverted_index.that | 218 |
| abstract_inverted_index.thus | 230 |
| abstract_inverted_index.used | 56 |
| abstract_inverted_index.with | 35, 208 |
| abstract_inverted_index.IFNβ | 179 |
| abstract_inverted_index.RNAs. | 13 |
| abstract_inverted_index.agar. | 98 |
| abstract_inverted_index.begin | 71 |
| abstract_inverted_index.cells | 51, 105, 188 |
| abstract_inverted_index.genes | 135 |
| abstract_inverted_index.knock | 62 |
| abstract_inverted_index.known | 142 |
| abstract_inverted_index.lines | 15, 69, 170 |
| abstract_inverted_index.media | 182 |
| abstract_inverted_index.miRNA | 30, 99, 110, 143, 201 |
| abstract_inverted_index.novel | 233 |
| abstract_inverted_index.other | 10 |
| abstract_inverted_index.shDcr | 187 |
| abstract_inverted_index.short | 11, 57 |
| abstract_inverted_index.tumor | 22, 37, 50, 80 |
| abstract_inverted_index.which | 140 |
| abstract_inverted_index.(ISG), | 136 |
| abstract_inverted_index.10(3); | 245 |
| abstract_inverted_index.AN3CA, | 163 |
| abstract_inverted_index.Cancer | 243 |
| abstract_inverted_index.DICER1 | 19, 25, 44, 64, 76, 82, 159, 204, 237 |
| abstract_inverted_index.IFNβ, | 146 |
| abstract_inverted_index.affect | 86 |
| abstract_inverted_index.cancer | 67, 168, 240 |
| abstract_inverted_index.caused | 90 |
| abstract_inverted_index.cells. | 198, 241 |
| abstract_inverted_index.effect | 234 |
| abstract_inverted_index.global | 40 |
| abstract_inverted_index.growth | 95 |
| abstract_inverted_index.levels | 26, 111, 129, 221 |
| abstract_inverted_index.mRNAs. | 120 |
| abstract_inverted_index.mature | 7 |
| abstract_inverted_index.miRNAs | 8 |
| abstract_inverted_index.normal | 174 |
| abstract_inverted_index.remain | 52 |
| abstract_inverted_index.report | 231 |
| abstract_inverted_index.stably | 61 |
| abstract_inverted_index.target | 144 |
| abstract_inverted_index.©2012 | 247 |
| abstract_inverted_index.Reduced | 24 |
| abstract_inverted_index.Several | 14 |
| abstract_inverted_index.changes | 28, 113, 126 |
| abstract_inverted_index.effects | 41 |
| abstract_inverted_index.hairpin | 58 |
| abstract_inverted_index.largely | 53 |
| abstract_inverted_index.overall | 107 |
| abstract_inverted_index.reduced | 43, 75, 200, 236 |
| abstract_inverted_index.suggest | 217 |
| abstract_inverted_index.trigger | 222 |
| abstract_inverted_index.activate | 192 |
| abstract_inverted_index.activity | 77 |
| abstract_inverted_index.elevated | 219 |
| abstract_inverted_index.enhanced | 91 |
| abstract_inverted_index.findings | 216 |
| abstract_inverted_index.function | 238 |
| abstract_inverted_index.majority | 138 |
| abstract_inverted_index.relative | 116 |
| abstract_inverted_index.response | 195, 225 |
| abstract_inverted_index.revealed | 106 |
| abstract_inverted_index.secreted | 180 |
| abstract_inverted_index.striking | 125 |
| abstract_inverted_index.unknown. | 54 |
| abstract_inverted_index.upstream | 149 |
| abstract_inverted_index.316–25. | 246 |
| abstract_inverted_index.Ishikawa, | 164 |
| abstract_inverted_index.abundance | 31, 48, 117 |
| abstract_inverted_index.decreases | 108 |
| abstract_inverted_index.determine | 73 |
| abstract_inverted_index.essential | 2 |
| abstract_inverted_index.implicate | 18 |
| abstract_inverted_index.increased | 157 |
| abstract_inverted_index.increases | 209 |
| abstract_inverted_index.knockdown | 83 |
| abstract_inverted_index.migration | 93 |
| abstract_inverted_index.noncoding | 12 |
| abstract_inverted_index.pre-miRNA | 220 |
| abstract_inverted_index.profiling | 102 |
| abstract_inverted_index.regulator | 150 |
| abstract_inverted_index.response, | 154 |
| abstract_inverted_index.aggressive | 36 |
| abstract_inverted_index.associated | 34, 207 |
| abstract_inverted_index.cytoplasm. | 214 |
| abstract_inverted_index.generation | 5 |
| abstract_inverted_index.knockdowns | 160, 205 |
| abstract_inverted_index.pre-miRNAs | 211 |
| abstract_inverted_index.processing | 202 |
| abstract_inverted_index.sequences. | 145 |
| abstract_inverted_index.sufficient | 190 |
| abstract_inverted_index.transcript | 47 |
| abstract_inverted_index.contributes | 78 |
| abstract_inverted_index.endometrial | 66, 167, 175 |
| abstract_inverted_index.phenotypes. | 38, 81 |
| abstract_inverted_index.suppressor. | 23 |
| abstract_inverted_index.<i>Mol | 242 |
| abstract_inverted_index.upregulation | 132 |
| abstract_inverted_index.EM-E6/E7/TERT | 186 |
| abstract_inverted_index.investigation | 17 |
| abstract_inverted_index.proliferation | 88 |
| abstract_inverted_index.significantly | 156 |
| abstract_inverted_index.EM-E6/E7/TERT. | 178 |
| abstract_inverted_index.IFN-stimulated | 134 |
| abstract_inverted_index.double-stranded | 227 |
| abstract_inverted_index.<div>Abstract<p>DICER1 | 0 |
| abstract_inverted_index.AACR</i>.</p></div> | 248 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5041123333 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 4 |
| corresponding_institution_ids | https://openalex.org/I117693200 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.4399999976158142 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.31331954 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |