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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...

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Autores principales: Kim, Eun-Ae, Jang, Ji-Hoon, Sung, Eon-Gi, Song, In-Hwan, Kim, Joo-Young, Lee, Tae-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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