SMAD4–201 transcript as a putative biomarker in colorectal cancer

Abstract

Background 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, 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). Methods Relative 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. Results The 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. Conclusion The 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.

Bioinformatic analysis and clinical diagnostic value of hsa_circ_0004099 in acute ischemic stroke

“…In the PPI network, the following eight core proteins were identified: SMAD4, HIF-1A, CDKN1B, CDK6, FOXO3, CTNNB1, KRAS, and NRAS. SMAD4 is a member of the SMAD family of encoded signal transduction proteins that are essential for maintaining tissue homeostasis and cell cycle regulation [35,36]. Amini et al [37] found that SMAD4 expression increased after IS, especially in those with the GG allele rs975903.…”

Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway

“…[3][4][5] SMAD Family Member 4 (SMAD4) is the core signalling transduction molecule in the transforming growth factorβ (TGF-β) signalling pathway. Loss of SMAD4 occurs in about 30% in CRC cases, 6 and its deficiency increases the risk of recurrence and poor prognosis of CRC patients. SMAD4 has two major structural domains, MH1, which binds to DNA, and MH2, which interacts with MH1 for transcriptional regulatory activity.…”