miR-181a-2 downregulates the E3 ubiquitin ligase CUL4A transcript and promotes cell proliferation
| Autor: | Venkateshwarlu Bandi, Sudhakar Baluchamy |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research DNA repair Down-Regulation 03 medical and health sciences Downregulation and upregulation Ubiquitin Humans 3' Untranslated Regions Cell Proliferation biology Cell growth HEK 293 cells Cell Cycle Hematology General Medicine Cell cycle Cullin Proteins Molecular biology Ubiquitin ligase MicroRNAs 030104 developmental biology HEK293 Cells Oncology biology.protein CUL4A |
| Zdroj: | Medical oncology (Northwood, London, England). 34(8) |
| ISSN: | 1559-131X |
| Popis: | MiR-181a-2 plays a major role in cell proliferation both positively and negatively depending on tissue type by targeting several regulators 3'UTR regions. We have predicted several targets for miR-181a-2 through computational approaches and characterized one its interesting target, CUL4A, an E3 ubiquitin ligase. CUL4A regulates diverse functions in the cells including DNA repair, DNA replication, cell cycle, genomic stability through polyubiquitination of target proteins. Deregulation of both miR-181a-2 and CUL4A are reported in many cancerous cells, but the functional link between them is unknown. We show that miR-181a-5p binds to 3'UTR of CUL4A and regulates its transcripts levels in HEK293 cells through overexpression studies. In addition, by using MTT and Neutral red assays, we showed that miR-181a-2 overexpression increased the proliferation in HEK293 cells. Moreover, cell cycle analysis using flow cytometer revealed that an increase in S-phase cells upon the overexpression of miR-181a-2. Though several miRNAs are known to downregulate the CUL4A levels, here we show that miR-181a-2 also participates in the downregulation of CUL4A. Taken together, our data demonstrated that miR-181a-2 increases the cell proliferation in HEK293 cells possibly through the downregulation of CUL4A. |
| Databáze: | OpenAIRE |
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