CSDE1 attenuates microRNA-mediated silencing of PMEPA1 in melanoma
| Autor: | Benjamin Goyer, Martin J. Simard, Louis-Mathieu Harvey, Lucie Germain, François Houle, Pavan Kumar Kakumani, Tanit Guitart, Fátima Gebauer |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Untranslated region Cancer Research Biology Metastasis 03 medical and health sciences 0302 clinical medicine microRNA Genetics medicine Humans Gene silencing RNA Messenger Melanoma Molecular Biology RNA-Binding Proteins Translation (biology) Cold-shock domain medicine.disease 3. Good health Cell biology MicroRNAs HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Argonaute Proteins |
| Zdroj: | Oncogene. 40:3231-3244 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | MicroRNAs and RNA-binding proteins (RBPs) primarily target the 3' UTR of mRNAs to control their translation and stability. However, their co-regulatory effects on specific mRNAs in physiology and disease are yet to be fully explored. CSDE1 is an RBP that promotes metastasis in melanoma and mechanisms underlying its oncogenic activities need to be completely defined. Here we report that CSDE1 interacts with specific miRNA-induced silencing complexes (miRISC) in melanoma. We find an association of CSDE1 with AGO2, the essential component of miRISC, which is facilitated by target mRNAs and depends on the first cold shock domain of CSDE1. Both CSDE1 and AGO2 bind to 3' UTR of PMEPA1. CSDE1 counters AGO2 binding, leading to an increase of PMEPA1 expression. We also identify a miRNA, miR-129-5p, that represses PMEPA1 expression in melanoma. Collectively, our results show that PMEPA1 promotes tumorigenic traits and that CSDE1 along with miR-129-5p/AGO2 miRISC act antagonistically to fine-tune PMEPA1 expression toward the progression of melanoma. |
| Databáze: | OpenAIRE |
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