ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
| Autor: | Marcelo G. Kazanietz, Mariana Cooke, Amjad Ahmed Aljagthmi, Martín Carlos Abba, Madhavi P. Kadakia, Natasha T. Hill, Weiwen Long |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Dp63
0301 basic medicine rac1 GTP-Binding Protein miR320 Cancer Research Medicina INVASION Immunology Blotting Western RAC1 Real-Time Polymerase Chain Reaction Article suppresses cells purl.org/becyt/ford/1 [https] 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Cell Line Tumor cancers Gene silencing Humans Neoplasm Invasiveness lcsh:QH573-671 Phosphorylation purl.org/becyt/ford/1.6 [https] Protein kinase C Regulation of gene expression Gene knockdown Chemistry lcsh:Cytology Wnt signaling pathway Cell Biology Oncogenes CANCER 3. Good health Cell biology Gene Expression Regulation Neoplastic MicroRNAs Protein Kinase C-delta 030104 developmental biology 030220 oncology & carcinogenesis Tumor Suppressor Protein p53 A431 cells Cell signalling Signal Transduction |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 9, Pp 1-14 (2019) SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 2041-4889 |
| Popis: | ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion. Facultad de Ciencias Médicas Centro de Investigaciones Inmunológicas Básicas y Aplicadas |
| Databáze: | OpenAIRE |
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