Int. J. Mol. Sci. 2018, 19(7), 1967; https://doi.org/10.3390/ijms19071967
miR-196a Is Able to Restore the Aggressive Phenotype of Annexin A1 Knock-Out in Pancreatic Cancer Cells by CRISPR/Cas9 Genome Editing
Raffaella Belvedere 1,†, Pasquale Saggese 2,†, Emanuela Pessolano 1, Domenico Memoli 2, Valentina Bizzarro 1, Francesca Rizzo 2
, Luca Parente 1, Alessandro Weisz 2 and Antonello Petrella 1,*
, Luca Parente 1, Alessandro Weisz 2 and Antonello Petrella 1,*
1
Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy
2
Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, via S. Allende, 1, 84081 Baronissi (SA), Italy
â€
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 28 May 2018 / Revised: 26 June 2018 / Accepted: 3 July 2018 / Published: 6 July 2018
(This article belongs to the Special Issue Cell and Molecular Biology of Pancreatic Disorders)
Abstract
Annexin A1 (ANXA1) is a Ca2+-binding protein that is involved in pancreatic cancer (PC) progression. It is able to mediate cytoskeletal organization maintaining a malignant phenotype. Our previous studies showed that ANXA1 Knock-Out (KO) MIA PaCa-2 cells partially lost their migratory and invasive capabilities and also the metastatization process appeared affected in vivo. Here, we investigated the microRNA (miRNA) profile in ANXA1 KO cells finding that the modification in miRNA expression suggests the significant involvement of ANXA1 in PC development. In this study, we focused on miR-196a which appeared down modulated in absence of ANXA1. This miRNA is a well known oncogenic factor in several tumour models and it is able to trigger the agents of the epithelial to mesenchymal transition (EMT), like ANXA1. Our results show that the reintroduction in ANXA1 KO cells of miR-196a through the mimic sequence restored the early aggressive phenotype of MIA PaCa-2. Then, ANXA1 seems to support the expression of miR-196a and its role. On the other hand, this miRNA is able to mediate cytoskeletal dynamics and other protein functions promoting PC cell migration and invasion. This work describes the correlation between ANXA1 and specific miRNA sequences, particularly miR-196a. These results could lead to further information on ANXA1 intracellular role in PC, explaining other aspects that are apart from its tumorigenic behaviour. View Full-TextKeywords:
annexin A1; pancreatic cancer; miR-196a-5p; EMT; biomarkers
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Belvedere, R.; Saggese, P.; Pessolano, E.; Memoli, D.; Bizzarro, V.; Rizzo, F.; Parente, L.; Weisz, A.; Petrella, A. miR-196a Is Able to Restore the Aggressive Phenotype of Annexin A1 Knock-Out in Pancreatic Cancer Cells by CRISPR/Cas9 Genome Editing. Int. J. Mol. Sci. 2018, 19, 1967.
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