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MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells
MicroRNAs (miRNAs) can be used to target a variety of human malignancies by targeting their oncogenes or tumor suppressor genes. Recent evidence has shown that miRNA-1208 (miR-1208) was rarely expressed in a variety of cancer cells, suggesting the possibility that miR-1208 functions as a tumor suppr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679220/ https://www.ncbi.nlm.nih.gov/pubmed/31331056 http://dx.doi.org/10.3390/ijms20143540 |
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author | Kim, Eun-Ae Jang, Ji-Hoon Sung, Eon-Gi Song, In-Hwan Kim, Joo-Young Lee, Tae-Jin |
author_facet | Kim, Eun-Ae Jang, Ji-Hoon Sung, Eon-Gi Song, In-Hwan Kim, Joo-Young Lee, Tae-Jin |
author_sort | Kim, Eun-Ae |
collection | PubMed |
description | MicroRNAs (miRNAs) can be used to target a variety of human malignancies by targeting their oncogenes or tumor suppressor genes. Recent evidence has shown that miRNA-1208 (miR-1208) was rarely expressed in a variety of cancer cells, suggesting the possibility that miR-1208 functions as a tumor suppressor gene. Herein, ectopic expression of miR-1208 induced the accumulation of sub-G1 populations and the cleavage of procaspase-3 and PARP, which could be prevented by pre-treatment with the pan-caspase inhibitor, Z-VAD. In addition, miR-1208 increased the susceptibility to cisplatin and TRAIL in Caki-1 cells. Luciferase reporter assay results showed that miR-1208 negatively regulates TBC1 domain containing kinase (TBCK) expression by binding to the miR-1208 binding sites in the 3′-untranslated region of TBCK. In addition, miR-1208 specifically repressed TBCK expression at the transcriptional level. In contrast, inhibition of endogenous miR-1208 by anti-miRs resulted in an increase in TBCK expression. Downregulation of TBCK induced by TBCK-specific siRNAs increased susceptibility to cisplatin and TRAIL. These findings suggest that miR-1208 acts as a tumor suppressor and targets TBCK directly, thus possessing great potential for use in renal cancer therapy. |
format | Online Article Text |
id | pubmed-6679220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66792202019-08-19 MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells Kim, Eun-Ae Jang, Ji-Hoon Sung, Eon-Gi Song, In-Hwan Kim, Joo-Young Lee, Tae-Jin Int J Mol Sci Article MicroRNAs (miRNAs) can be used to target a variety of human malignancies by targeting their oncogenes or tumor suppressor genes. Recent evidence has shown that miRNA-1208 (miR-1208) was rarely expressed in a variety of cancer cells, suggesting the possibility that miR-1208 functions as a tumor suppressor gene. Herein, ectopic expression of miR-1208 induced the accumulation of sub-G1 populations and the cleavage of procaspase-3 and PARP, which could be prevented by pre-treatment with the pan-caspase inhibitor, Z-VAD. In addition, miR-1208 increased the susceptibility to cisplatin and TRAIL in Caki-1 cells. Luciferase reporter assay results showed that miR-1208 negatively regulates TBC1 domain containing kinase (TBCK) expression by binding to the miR-1208 binding sites in the 3′-untranslated region of TBCK. In addition, miR-1208 specifically repressed TBCK expression at the transcriptional level. In contrast, inhibition of endogenous miR-1208 by anti-miRs resulted in an increase in TBCK expression. Downregulation of TBCK induced by TBCK-specific siRNAs increased susceptibility to cisplatin and TRAIL. These findings suggest that miR-1208 acts as a tumor suppressor and targets TBCK directly, thus possessing great potential for use in renal cancer therapy. MDPI 2019-07-19 /pmc/articles/PMC6679220/ /pubmed/31331056 http://dx.doi.org/10.3390/ijms20143540 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Eun-Ae Jang, Ji-Hoon Sung, Eon-Gi Song, In-Hwan Kim, Joo-Young Lee, Tae-Jin MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells |
title | MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells |
title_full | MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells |
title_fullStr | MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells |
title_full_unstemmed | MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells |
title_short | MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells |
title_sort | mir-1208 increases the sensitivity to cisplatin by targeting tbck in renal cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679220/ https://www.ncbi.nlm.nih.gov/pubmed/31331056 http://dx.doi.org/10.3390/ijms20143540 |
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