Next Article in Journal
Phenotype-Driven Diagnostic of PTEN Hamartoma Tumor Syndrome: Macrocephaly, But Neither Height nor Weight Development, Is the Important Trait in Children
Previous Article in Journal
Functional Toll-Like Receptors (TLRs) Are Expressed by a Majority of Primary Human Acute Myeloid Leukemia Cells and Inducibility of the TLR Signaling Pathway Is Associated with a More Favorable Phenotype
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle

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

Department of Pharmacology and New Drug Development Research Institute, Chonbuk National University Medical School, Jeonju 54896, Korea
Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration (RDA), Wanju-gun, Chonbuk 54875, Korea
Department of Chemistry, Inha University, Incheon 402-751, Korea
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;
Received: 18 May 2019 / Revised: 28 June 2019 / Accepted: 8 July 2019 / Published: 11 July 2019
PDF [2952 KB, uploaded 11 July 2019]


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

Graphical abstract

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).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top