Abstract
BackgroundTranscripts with alternative 5′-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4–201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC).MethodsRelative abundance of SMAD4–201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC.ResultsThe relative abundance of SMAD4–201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4–201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4–202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4–201 and SMAD4–202.ConclusionThe expression profile of SMAD4–201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis.
Highlights
Transcripts with alternative 5′-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, executing complex regulation of developmental, physiological and pathological processes
The relative abundance of the transcript SMAD family member 4 (SMAD4)–201 was analyzed in human malignant and non-malignant cell lines and tissue samples in order to explore its translational potential for colorectal cancer diagnostics
The relative abundance of SMAD4–201 was calculated as a portion of total SMAD4 expression, which was measured using primers that anneal to the beginning of the coding sequence
Summary
Transcripts with alternative 5′-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. SMAD family member 4 (SMAD4) is essential for the maintenance of tissue homeostasis and cell cycle regulation. This molecule is a key tumor suppressor in human gastrointestinal tissues and its expression was established as altered in various types of solid tumors [1]. Loss of tumor suppressor SMAD4 occurs in about 30% of colorectal cancer (CRC) cases [3]. Posttranscriptional regulation of the SMAD4 gene can be involved in colorectal carcinogenesis, Babic et al BMC Cancer (2022) 22:72
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