miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer
Desmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell polarity and disorganized tissue architecture typical of colorectal cancer (CRC). The aim of this study was to investigate and characteri...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/17084 |
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| author | Emanuele Piccinno Viviana Scalavino Raffaele Armentano Gianluigi Giannelli Grazia Serino |
| author_facet | Emanuele Piccinno Viviana Scalavino Raffaele Armentano Gianluigi Giannelli Grazia Serino |
| author_sort | Emanuele Piccinno |
| collection | DOAJ |
| description | Desmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell polarity and disorganized tissue architecture typical of colorectal cancer (CRC). The aim of this study was to investigate and characterize the effect of miR-195-5p on desmosomal junction regulation in CRC. In detail, we proposed to investigate the deregulation of miR-195-5p and <i>JUP</i>, a gene target that encodes a desmosome component in CRC patients. JUP closely interacts with desmosomal cadherins, and downstream, it regulates several intracellular transduction factors. We restored the miR-195-5p levels by transient transfection in colonic epithelial cells to examine the effects of miR-195-5p on JUP mRNA and protein expression. The JUP regulation by miR-195-5p, in turn, determined a modulation of desmosome cadherins (Desmoglein 2 and Desmocollin 2). Furthermore, we focused on whether the miR-195-5p gain of function was also able to modulate the expression of key components of Wnt signaling, such as NLK, LEF1 and Cyclin D1. In conclusion, we have identified a novel mechanism controlled by miR-195-5p in the regulation of adhesive junctions, suggesting its potential clinical relevance for future miRNA-based therapy in CRC. |
| first_indexed | 2024-03-09T01:49:03Z |
| format | Article |
| id | doaj.art-8ed473928bf14ee4bd113f7681bd8e2c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:49:03Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ed473928bf14ee4bd113f7681bd8e2c2023-12-08T15:18:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124231708410.3390/ijms242317084miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal CancerEmanuele Piccinno0Viviana Scalavino1Raffaele Armentano2Gianluigi Giannelli3Grazia Serino4National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, ItalyNational Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, ItalyNational Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, ItalyNational Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, ItalyNational Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, ItalyDesmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell polarity and disorganized tissue architecture typical of colorectal cancer (CRC). The aim of this study was to investigate and characterize the effect of miR-195-5p on desmosomal junction regulation in CRC. In detail, we proposed to investigate the deregulation of miR-195-5p and <i>JUP</i>, a gene target that encodes a desmosome component in CRC patients. JUP closely interacts with desmosomal cadherins, and downstream, it regulates several intracellular transduction factors. We restored the miR-195-5p levels by transient transfection in colonic epithelial cells to examine the effects of miR-195-5p on JUP mRNA and protein expression. The JUP regulation by miR-195-5p, in turn, determined a modulation of desmosome cadherins (Desmoglein 2 and Desmocollin 2). Furthermore, we focused on whether the miR-195-5p gain of function was also able to modulate the expression of key components of Wnt signaling, such as NLK, LEF1 and Cyclin D1. In conclusion, we have identified a novel mechanism controlled by miR-195-5p in the regulation of adhesive junctions, suggesting its potential clinical relevance for future miRNA-based therapy in CRC.https://www.mdpi.com/1422-0067/24/23/17084microRNACRCJUPγ-cateninmiR-195-5pdesmosome |
| spellingShingle | Emanuele Piccinno Viviana Scalavino Raffaele Armentano Gianluigi Giannelli Grazia Serino miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer International Journal of Molecular Sciences microRNA CRC JUP γ-catenin miR-195-5p desmosome |
| title | miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer |
| title_full | miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer |
| title_fullStr | miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer |
| title_full_unstemmed | miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer |
| title_short | miR-195-5p as Regulator of γ-Catenin and Desmosome Junctions in Colorectal Cancer |
| title_sort | mir 195 5p as regulator of γ catenin and desmosome junctions in colorectal cancer |
| topic | microRNA CRC JUP γ-catenin miR-195-5p desmosome |
| url | https://www.mdpi.com/1422-0067/24/23/17084 |
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