Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer
Prostate cancer is a major health problem worldwide. MiR-183 is an oncomiR and a candidate biomarker in prostate cancer, affecting various pathways responsible for disease initiation and progression. We sought to discover the most relevant processes controlled by miR-183 through an unbiased transcri...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Non-Coding RNA |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2311-553X/8/1/11 |
| _version_ | 1797477551644344320 |
|---|---|
| author | Carolina Oliveira-Rizzo María Carolina Ottati Rafael Sebastián Fort Santiago Chavez Juan Manuel Trinidad Andrés DiPaolo Beatriz Garat José Roberto Sotelo-Silveira María Ana Duhagon |
| author_facet | Carolina Oliveira-Rizzo María Carolina Ottati Rafael Sebastián Fort Santiago Chavez Juan Manuel Trinidad Andrés DiPaolo Beatriz Garat José Roberto Sotelo-Silveira María Ana Duhagon |
| author_sort | Carolina Oliveira-Rizzo |
| collection | DOAJ |
| description | Prostate cancer is a major health problem worldwide. MiR-183 is an oncomiR and a candidate biomarker in prostate cancer, affecting various pathways responsible for disease initiation and progression. We sought to discover the most relevant processes controlled by miR-183 through an unbiased transcriptomic approach using prostate cell lines and patient tissues to identify miR-183 responsive genes and pathways. Gain of function experiments, reporter gene assays, and transcript and protein measurements were conducted to validate predicted functional effects and protein mediators. A total of 135 candidate miR-183 target genes overrepresenting cell adhesion terms were inferred from the integrated transcriptomic analysis. Cell attachment, spreading assays and focal adhesion quantification of miR-183-overexpressing cells confirmed the predicted reduction in cell adhesion. <i>ITGB1</i> was validated as a major target of repression by miR-183 as well as a mediator of cell adhesion in response to miR-183. The reporter gene assay and PAR-CLIP read mapping suggest that ITGB1 may be a direct target of miR-183. The negative correlation between miR-183 and <i>ITGB1</i> expression in prostate cancer cohorts supports their interaction in the clinical set. Overall, cell adhesion was uncovered as a major pathway controlled by miR-183 in prostate cancer, and ITGB1 was identified as a relevant mediator of this effect. |
| first_indexed | 2024-03-09T21:19:18Z |
| format | Article |
| id | doaj.art-e2af15bcb6e4493ab61ba8b74f9dd0c1 |
| institution | Directory Open Access Journal |
| issn | 2311-553X |
| language | English |
| last_indexed | 2024-03-09T21:19:18Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Non-Coding RNA |
| spelling | doaj.art-e2af15bcb6e4493ab61ba8b74f9dd0c12023-11-23T21:27:15ZengMDPI AGNon-Coding RNA2311-553X2022-01-01811110.3390/ncrna8010011Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate CancerCarolina Oliveira-Rizzo0María Carolina Ottati1Rafael Sebastián Fort2Santiago Chavez3Juan Manuel Trinidad4Andrés DiPaolo5Beatriz Garat6José Roberto Sotelo-Silveira7María Ana Duhagon8Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayDepartamento de Genómica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayDepartamento de Genómica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, UruguayProstate cancer is a major health problem worldwide. MiR-183 is an oncomiR and a candidate biomarker in prostate cancer, affecting various pathways responsible for disease initiation and progression. We sought to discover the most relevant processes controlled by miR-183 through an unbiased transcriptomic approach using prostate cell lines and patient tissues to identify miR-183 responsive genes and pathways. Gain of function experiments, reporter gene assays, and transcript and protein measurements were conducted to validate predicted functional effects and protein mediators. A total of 135 candidate miR-183 target genes overrepresenting cell adhesion terms were inferred from the integrated transcriptomic analysis. Cell attachment, spreading assays and focal adhesion quantification of miR-183-overexpressing cells confirmed the predicted reduction in cell adhesion. <i>ITGB1</i> was validated as a major target of repression by miR-183 as well as a mediator of cell adhesion in response to miR-183. The reporter gene assay and PAR-CLIP read mapping suggest that ITGB1 may be a direct target of miR-183. The negative correlation between miR-183 and <i>ITGB1</i> expression in prostate cancer cohorts supports their interaction in the clinical set. Overall, cell adhesion was uncovered as a major pathway controlled by miR-183 in prostate cancer, and ITGB1 was identified as a relevant mediator of this effect.https://www.mdpi.com/2311-553X/8/1/11cancermicroRNAfocal adhesionmiR-183prostateITGB1 |
| spellingShingle | Carolina Oliveira-Rizzo María Carolina Ottati Rafael Sebastián Fort Santiago Chavez Juan Manuel Trinidad Andrés DiPaolo Beatriz Garat José Roberto Sotelo-Silveira María Ana Duhagon Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer Non-Coding RNA cancer microRNA focal adhesion miR-183 prostate ITGB1 |
| title | Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer |
| title_full | Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer |
| title_fullStr | Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer |
| title_full_unstemmed | Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer |
| title_short | Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer |
| title_sort | hsa mir 183 5p modulates cell adhesion by repression of i itgb1 i expression in prostate cancer |
| topic | cancer microRNA focal adhesion miR-183 prostate ITGB1 |
| url | https://www.mdpi.com/2311-553X/8/1/11 |
| work_keys_str_mv | AT carolinaoliveirarizzo hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT mariacarolinaottati hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT rafaelsebastianfort hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT santiagochavez hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT juanmanueltrinidad hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT andresdipaolo hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT beatrizgarat hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT joserobertosotelosilveira hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer AT mariaanaduhagon hsamir1835pmodulatescelladhesionbyrepressionofiitgb1iexpressioninprostatecancer |