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Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC

1
Department of Pharmacology and New Drug Development Research Institute, Chonbuk National University Medical School, Jeonju 54896, Korea
2
Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration (RDA), Wanju-gun, Chonbuk 54875, Korea
3
Department of Chemistry, Inha University, Incheon 402-751, Korea
4
College of Dentistry, Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(7), 974; https://doi.org/10.3390/cancers11070974
Received: 18 May 2019 / Revised: 28 June 2019 / Accepted: 8 July 2019 / Published: 11 July 2019
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Abstract

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (−133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer. View Full-Text
Keywords: TMBIM6; promoter; transcriptional regulation; Sp1; PKC; cancer TMBIM6; promoter; transcriptional regulation; Sp1; PKC; cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Junjappa, R.P.; Kim, H.-K.; Park, S.Y.; Bhattarai, K.R.; Kim, K.-W.; Soh, J.-W.; Kim, H.-R.; Chae, H.-J. Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC. Cancers 2019, 11, 974.

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