Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway
Akt1 suppression in advanced cancers has been indicated to promote metastasis. Our understanding of how Akt1 orchestrates this is incomplete. Using the NanoString<sup>®</sup>-based miRNA and mRNA profiling of PC3 and DU145 cells, and subsequent data analysis using the DIANA-mirPath, dbEM...
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/7/1625 |
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| author | Abdulrahman Alwhaibi Varun Parvathagiri Arti Verma Sandeep Artham Mir S. Adil Payaningal R. Somanath |
| author_facet | Abdulrahman Alwhaibi Varun Parvathagiri Arti Verma Sandeep Artham Mir S. Adil Payaningal R. Somanath |
| author_sort | Abdulrahman Alwhaibi |
| collection | DOAJ |
| description | Akt1 suppression in advanced cancers has been indicated to promote metastasis. Our understanding of how Akt1 orchestrates this is incomplete. Using the NanoString<sup>®</sup>-based miRNA and mRNA profiling of PC3 and DU145 cells, and subsequent data analysis using the DIANA-mirPath, dbEMT, nCounter, and Ingenuity<sup>®</sup> databases, we identified the miRNAs and associated genes responsible for Akt1-mediated prostate cancer (PCa) epithelial-to-mesenchymal transition (EMT). Akt1 loss in PC3 and DU145 cells primarily induced changes in the miRNAs and mRNAs regulating EMT genes. These include increased miR-199a-5p and decreased let-7a-5p expression associated with increased TGFβ-R1 expression. Treatment with locked nucleic acid (LNA) miR-199a-5p inhibitor and/or let-7a-5p mimic induced expression changes in EMT genes correlating to their anticipated effects on PC3 and DU145 cell motility, invasion, and TGFβ-R1 expression. A correlation between increased miR-199a-5p and TGFβ-R1 expression with reduced let-7a-5p was also observed in high Gleason score PCa patients in the cBioportal database analysis. Collectively, our studies show the effect of Akt1 suppression in advanced PCa on EMT modulating miRNA and mRNA expression changes and highlight the potential benefits of miR-199a-5p and let-7a-5p in therapy and/or early screening of mPCa. |
| first_indexed | 2024-03-09T12:05:03Z |
| format | Article |
| id | doaj.art-c1cf97a94b0d4dd882c0199ed09f8471 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T12:05:03Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c1cf97a94b0d4dd882c0199ed09f84712023-11-30T22:59:44ZengMDPI AGCancers2072-66942022-03-01147162510.3390/cancers14071625Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β PathwayAbdulrahman Alwhaibi0Varun Parvathagiri1Arti Verma2Sandeep Artham3Mir S. Adil4Payaningal R. Somanath5Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USAClinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USAClinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USAClinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USAClinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USAClinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USAAkt1 suppression in advanced cancers has been indicated to promote metastasis. Our understanding of how Akt1 orchestrates this is incomplete. Using the NanoString<sup>®</sup>-based miRNA and mRNA profiling of PC3 and DU145 cells, and subsequent data analysis using the DIANA-mirPath, dbEMT, nCounter, and Ingenuity<sup>®</sup> databases, we identified the miRNAs and associated genes responsible for Akt1-mediated prostate cancer (PCa) epithelial-to-mesenchymal transition (EMT). Akt1 loss in PC3 and DU145 cells primarily induced changes in the miRNAs and mRNAs regulating EMT genes. These include increased miR-199a-5p and decreased let-7a-5p expression associated with increased TGFβ-R1 expression. Treatment with locked nucleic acid (LNA) miR-199a-5p inhibitor and/or let-7a-5p mimic induced expression changes in EMT genes correlating to their anticipated effects on PC3 and DU145 cell motility, invasion, and TGFβ-R1 expression. A correlation between increased miR-199a-5p and TGFβ-R1 expression with reduced let-7a-5p was also observed in high Gleason score PCa patients in the cBioportal database analysis. Collectively, our studies show the effect of Akt1 suppression in advanced PCa on EMT modulating miRNA and mRNA expression changes and highlight the potential benefits of miR-199a-5p and let-7a-5p in therapy and/or early screening of mPCa.https://www.mdpi.com/2072-6694/14/7/1625Akt1miR-199a-5plet-7a-5pepithelial-to-mesenchymal transitionprostate cancer |
| spellingShingle | Abdulrahman Alwhaibi Varun Parvathagiri Arti Verma Sandeep Artham Mir S. Adil Payaningal R. Somanath Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway Cancers Akt1 miR-199a-5p let-7a-5p epithelial-to-mesenchymal transition prostate cancer |
| title | Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway |
| title_full | Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway |
| title_fullStr | Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway |
| title_full_unstemmed | Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway |
| title_short | Regulation of Let-7a-5p and miR-199a-5p Expression by Akt1 Modulates Prostate Cancer Epithelial-to-Mesenchymal Transition via the Transforming Growth Factor-β Pathway |
| title_sort | regulation of let 7a 5p and mir 199a 5p expression by akt1 modulates prostate cancer epithelial to mesenchymal transition via the transforming growth factor β pathway |
| topic | Akt1 miR-199a-5p let-7a-5p epithelial-to-mesenchymal transition prostate cancer |
| url | https://www.mdpi.com/2072-6694/14/7/1625 |
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