Dysregulation of transcripts SMAD4-209 and SMAD4-213 and their respective promoters in colon cancer cell lines
2024
Authors:
Babić, TamaraUgrin, Milena
Jeremić, Sanja
Kojić, Milan
Dinić, Jelena
Banović Djeri, Bojana
Zoidakis, Jerome
Nikolić, Aleksandra
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Background: The pervasive role of alternative promoters in context-specific isoform expression and the importance of promoter choice over its level of transcriptional activity have been recently implied based on pan-cancer in silico studies. We aimed to explore this phenomenon at the cellular level on the example of a major tumor suppressor SMAD4 in search of molecular mechanisms in colorectal cancer that could be exploited for novel biomarkers or therapeutic approaches.
Methods: Multi-omics technologies, in silico tools and in vitro functional assays were applied to analyze the transcripts expression and the alternative promoters' function of the SMAD4 gene in colon cell lines HCEC-1CT, HCT116, DLD-1, SW480 and SW620.
Results: High expression of the transcript SMAD4-213 emerged as a hallmark of colon cancer cells, while in silico tools point to its possible additional role and potential for sponging miRNAs. Based on the observed dysregulation of SMAD4-209 and SMAD4-213 in malignant vs. non-malignant colon cells, we propose that their expression ratio might be a solid biomarker candidate for colorectal cancer detection.
Conclusions: A differential pattern of the respective promoters' activity was observed that corresponds to the expression of transcripts, confirming the role of alternative promoters in context-specific isoform expression. The investigated SMAD4 promoters and transcripts harbor translational potential that should be further investigated.
Keywords:
SMAD4; transcriptional regulation; alternative promoter; colorectal cancer; transcriptSource:
Journal of Cancer, 2024, 15, 15, 5118-5131Funding / projects:
- SENSOGENE - Cancer Biosensors Based on Gene Regulatory Elements (RS-ScienceFundRS-Promis-6052315)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)