Cargando…

Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells

(1) Background: The hedgehog (HH) signaling pathway is a key regulator of embryonic patterning, tissue regeneration, stem cell renewal, and cancer growth. The smoothened (SMO) protein regulates the HH signaling pathway and has demonstrated oncogenic activity. (2) Methods: To clarify the role of the...

Descripción completa

Detalles Bibliográficos
Autores principales: Lou, Hong, Li, Hongchuan, Huehn, Andrew R., Tarasova, Nadya I., Saleh, Bahara, Anderson, Stephen K., Dean, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464114/
https://www.ncbi.nlm.nih.gov/pubmed/32784501
http://dx.doi.org/10.3390/cancers12082219
_version_ 1783577289747857408
author Lou, Hong
Li, Hongchuan
Huehn, Andrew R.
Tarasova, Nadya I.
Saleh, Bahara
Anderson, Stephen K.
Dean, Michael
author_facet Lou, Hong
Li, Hongchuan
Huehn, Andrew R.
Tarasova, Nadya I.
Saleh, Bahara
Anderson, Stephen K.
Dean, Michael
author_sort Lou, Hong
collection PubMed
description (1) Background: The hedgehog (HH) signaling pathway is a key regulator of embryonic patterning, tissue regeneration, stem cell renewal, and cancer growth. The smoothened (SMO) protein regulates the HH signaling pathway and has demonstrated oncogenic activity. (2) Methods: To clarify the role of the HH signaling pathway in tumorigenesis, the expression profile of key HH signaling molecules, including SMO, PTCH1, GLI1, GLI2, and GLI3, were determined in 33 cancer cell lines and normal prostate cells and tissues. We performed a computational analysis of the upstream region of the SMO gene to identify the regulatory elements. (3) Results: Three potential CpG islands and several putative SMO promoter elements were identified. Luciferase reporter assays mapped key SMO promoter elements, and functional binding sites for SP1, AP1, CREB, and AP-2α transcription factors in the core SMO promoter region were confirmed. A hypermethylated SMO promoter was identified in several cancer cell lines suggesting an important role for epigenetic silencing of SMO expression in certain cancer cells. (4) Discussion: These results have important implications for our understanding of regulatory mechanisms controlling HH pathway activity and the molecular basis of SMO gene function. Moreover, this study may prove valuable for future research aimed at producing therapeutic downregulation of SMO expression in cancer cells.
format Online
Article
Text
id pubmed-7464114
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74641142020-09-04 Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells Lou, Hong Li, Hongchuan Huehn, Andrew R. Tarasova, Nadya I. Saleh, Bahara Anderson, Stephen K. Dean, Michael Cancers (Basel) Article (1) Background: The hedgehog (HH) signaling pathway is a key regulator of embryonic patterning, tissue regeneration, stem cell renewal, and cancer growth. The smoothened (SMO) protein regulates the HH signaling pathway and has demonstrated oncogenic activity. (2) Methods: To clarify the role of the HH signaling pathway in tumorigenesis, the expression profile of key HH signaling molecules, including SMO, PTCH1, GLI1, GLI2, and GLI3, were determined in 33 cancer cell lines and normal prostate cells and tissues. We performed a computational analysis of the upstream region of the SMO gene to identify the regulatory elements. (3) Results: Three potential CpG islands and several putative SMO promoter elements were identified. Luciferase reporter assays mapped key SMO promoter elements, and functional binding sites for SP1, AP1, CREB, and AP-2α transcription factors in the core SMO promoter region were confirmed. A hypermethylated SMO promoter was identified in several cancer cell lines suggesting an important role for epigenetic silencing of SMO expression in certain cancer cells. (4) Discussion: These results have important implications for our understanding of regulatory mechanisms controlling HH pathway activity and the molecular basis of SMO gene function. Moreover, this study may prove valuable for future research aimed at producing therapeutic downregulation of SMO expression in cancer cells. MDPI 2020-08-08 /pmc/articles/PMC7464114/ /pubmed/32784501 http://dx.doi.org/10.3390/cancers12082219 Text en © 2020 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
Lou, Hong
Li, Hongchuan
Huehn, Andrew R.
Tarasova, Nadya I.
Saleh, Bahara
Anderson, Stephen K.
Dean, Michael
Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells
title Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells
title_full Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells
title_fullStr Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells
title_full_unstemmed Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells
title_short Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells
title_sort genetic and epigenetic regulation of the smoothened gene (smo) in cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464114/
https://www.ncbi.nlm.nih.gov/pubmed/32784501
http://dx.doi.org/10.3390/cancers12082219
work_keys_str_mv AT louhong geneticandepigeneticregulationofthesmoothenedgenesmoincancercells
AT lihongchuan geneticandepigeneticregulationofthesmoothenedgenesmoincancercells
AT huehnandrewr geneticandepigeneticregulationofthesmoothenedgenesmoincancercells
AT tarasovanadyai geneticandepigeneticregulationofthesmoothenedgenesmoincancercells
AT salehbahara geneticandepigeneticregulationofthesmoothenedgenesmoincancercells
AT andersonstephenk geneticandepigeneticregulationofthesmoothenedgenesmoincancercells
AT deanmichael geneticandepigeneticregulationofthesmoothenedgenesmoincancercells