Mononucleotide repeats in the SMAD4 gene promoter in colon carcinoma tissue of Croatian patients

Nikolić, Aleksandra; Čačev, Tamara; Aralica, Gorana; Hadžija, Mirko; Kapitanović, Sanja; Radojković, Dragica

doi:10.1016/j.yexmp.2015.02.008

Cited by 4 publications

(2 citation statements)

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“…More recent studies indicate mutations of alternative promoters as a mechanism leading to aberrant usage of one promoter over the other [37,38]. Functionally relevant mutations in alternative SMAD4 promoters were shown to be quite rare, so in the case of this tumor suppressor other mechanisms and interactions with the cellular proteotranscriptome may be more relevant [39][40][41][42]. The cellular content of transcripts with alternative 5′-UTRs results from a variety of factors and the exact mechanisms behind the process of aberrant alternative transcription initiation in cancer remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

SMAD4–201 transcript as a putative biomarker in colorectal cancer

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

SMAD4–201 transcript as a putative biomarker in colorectal cancer

et al. 2022

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“…Two somatic mutations that disturb transcription were found in endometrial carcinoma (11). Another somatic alteration in this region was found in tumor tissues of patients with pancreatic, colorectal and endometrial cancer and it was shown to significantly reduce promoter activity of this segment (6,7,12). Relatively small number of studies analyzed methylation status of the SMAD4 5' regulatory region, mostly in gastrointestinal cancers, and it was not found to be a major mechanism of SMAD4 inactivation (9,13,14,15).…”

Section: Introductionmentioning

confidence: 99%

Analysis of smad4 gene promoter methylation in pancreatic and endometrial cancers

et al. 2017

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Background. Promoter hypermethylation of the SMAD4 gene has been registered in some cancer types, but in general doesn't appear to be a frequent event in carcinogenesis. However, only a few published studies deal with this topic and not many cancer types have been analyzed. The aim of this study was to establish SMAD4 gene promoter methylation status in pancreatic and endometrial cancers. Methods. Patients included in the study (62 subjects) were diagnosed and surgically treated at the University of Belgrade, Clinical Center of Serbia. Patients with pancreatic carcinoma (17 subjects) underwent surgical removal of the pancreatic adenocarcinoma at the First Surgical Clinic, while the patients with endometrial carcinoma (45 subjects) underwent hysterectomy with adnexectomy at the Institute for Gynecology and Obstetrics. Extraction of DNA from fresh tissue samples was performed and the methylation status of the SMAD4 gene promoter was studied by a previously designed PCR-based HpaII and MspI restriction enzyme assay. The resulting PCR products were analyzed by electrophoresis in 2% agarose gels. Results. Neither of the analyzed samples was found to be hypermethylated. Conclusion. This is the first report on SMAD4 methylation status in pancreatic and endometrial tumor specimens, and supports the viewpoint that SMAD4 hypermethylation is not a common event in malignant tumors. Nevertheless, promoter hypermethylation remains a candidate mechanism for SMAD4 inactivation in malignant tissue as a potential cause of decreased or lost SMAD4 expression in certain tumor types, and should be further investigated in different tumor types and larger cohorts of patients.

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A non-invasive cancer gene detection technique using FLANN based adaptive filter

Roy

Barman

2018

Microsyst Technol

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Mononucleotide repeats in the SMAD4 gene promoter in colon carcinoma tissue of Croatian patients

Cited by 4 publications

References 21 publications

SMAD4–201 transcript as a putative biomarker in colorectal cancer

SMAD4–201 transcript as a putative biomarker in colorectal cancer

Analysis of smad4 gene promoter methylation in pancreatic and endometrial cancers

A non-invasive cancer gene detection technique using FLANN based adaptive filter

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