Tamara Babic, Milena Ugrin, Sanja Jeremic, Milan Kojic, Jelena Dinic, Bojana Banovic Djeri, Jerome Zoidakis, Aleksandra Nikolic
{"title":"Dysregulation of transcripts SMAD4-209 and SMAD4-213 and their respective promoters in colon cancer cell lines.","authors":"Tamara Babic, Milena Ugrin, Sanja Jeremic, Milan Kojic, Jelena Dinic, Bojana Banovic Djeri, Jerome Zoidakis, Aleksandra Nikolic","doi":"10.7150/jca.98911","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> 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 <i>in silico</i> 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. <b>Methods:</b> Multi-omics technologies, <i>in silico</i> tools and <i>in vitro</i> 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. <b>Results:</b> High expression of the transcript SMAD4-213 emerged as a hallmark of colon cancer cells, while <i>in silico</i> 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. <b>Conclusions:</b> 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 <i>SMAD4</i> promoters and transcripts harbor translational potential that should be further investigated.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310865/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/jca.98911","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.