SMAD4 gene promoter mutations in patients with thyroid tumors

Nikolić, Aleksandra; Ristanovic, Momcilo; Živaljević, Vladan; Rankov, Aleksandra Divac; Radojković, Dragica; Paunović, Ivan

doi:10.1016/j.yexmp.2015.06.005

Cited by 9 publications

(6 citation statements)

References 30 publications

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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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“…Molecular evens downstream of over-expressed miR-146b were also studied in the context of thyroid cancer [38]. A list of the direct targets of miR-146b includes several genes involved in the maintenance of malignant phenotypes and invasive properties ( Figure 5): PHKB [39,40], SMAD4 [41,42], PAX8 [43], ZNRF3 [44] and ST8SIA4 [45]. The last two miR-146b downstream pathways are shown to be involved in thyroid carcinogenesis in independent studies.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal Dysregulation of MiR-146b and MiR-451 Contributes in Malignant Phenotype of Follicular Thyroid Tumor

Knyazeva

Korobkina

Karizky

et al. 2020

IJMS

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Over the last few years, incidental thyroid nodules are being diagnosed with increasing frequency with the use of highly sensitive imaging techniques. The ultrasound thyroid gland examination, followed by the fine-needle aspiration cytology is the standard diagnostic approach. However, in cases of the follicular nature of nodules, cytological diagnosis is not enough. Analysis of miRNAs in the biopsy presents a promising approach. Increasing our knowledge of miRNA’s role in follicular carcinogenesis, and development of the appropriate the miRNA analytical technologies are required to implement miRNA-based tests in clinical practice. We used material from follicular thyroid nodes (n.84), grouped in accordance with their invasive properties. The invasion-associated miRNAs expression alterations were assayed. Expression data were confirmed by highly sensitive two-tailed RT-qPCR. Reciprocally dysregulated miRNAs pair concentration ratios were explored as a diagnostic parameter using receiver operation curve (ROC) analysis. A new bioinformatics method (MiRImpact) was applied to evaluate the biological significance of the observed expression alterations. Coupled experimental and computational approaches identified reciprocal dysregulation of miR-146b and miR-451 as important attributes of follicular cell malignant transformation and follicular thyroid cancer progression. Thus, evaluation of combined dysregulation of miRNAs relevant to invasion and metastasis can help to distinguish truly malignant follicular thyroid cancer from indolent follicular adenoma.

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“…The most common gene mutations were found in TGFβR-II, which contains a 10-base pair polyadenylic acid repeat region in its coding sequence (66). SMADs were involved in the anti-tumor process, however gene mutations in SMAD were observed in cases of breast, thyroid, ovarian, and colorectal cancer (55,(67)(68)(69). In fact, invasive tumors retain the core components of TGF-β signaling, which they appear to give priority to obtaining gene mutations in the core components, thereby producing resistance to TGF-β signaling-mediated growth arrest.…”

Section: The Promotion Of Tgf-β Signaling In Tumorsmentioning

confidence: 99%

A narrative review of the relationship between TGF-β signaling and gynecological malignant tumor

Luo¹,

Huang²,

Li³

et al. 2021

Ann Transl Med

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Objective: This paper reviews the association between transforming growth factor-β (TGF-β) and its receptor and tumor, focusing on gynecological malignant tumors. we hope to provide more methods to help increase the potential of TGF-β signaling targeted treatment of specific cancers.Background: The occurrence of a malignant tumor is a complex process of multi-step, multi-gene regulation, and its progression is affected by various components of the tumor cells and/or tumor microenvironment. The occurrence of gynecological diseases not only affect women's health, but also bring some troubles to their normal life. Especially when gynecological malignant tumors occur, the situation is more serious, which will endanger the lives of patients. Due to differences in environmental and economic conditions, not all women have access to assistance and treatment specifically meeting their needs. TGF-β is a multi-potent growth factor that maintains homeostasis in mammals by inhibiting cell growth and promoting apoptosis in vivo. TGF-β signaling is fundamental to inflammatory disease and favors the emergence of tumors, and it also plays an important role in immunosuppression in the tumor microenvironment. In the early stages of the tumor, TGF-β acts as a tumor inhibitor, whereas in advanced tumors, mutations or deletion of the TGF-β signaling core component initiate neogenesis.Methods: Literatures about TGF-β and gynecological malignant tumor were extensively reviewed to analyze and discuss. Conclusions:We discussed the role of TGF-β signaling in different types of gynecological tumor cells, thus demonstrating that targeted TGF-β signaling may be an effective tumor treatment strategy.

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SMAD4 gene promoter mutations in patients with thyroid tumors

Cited by 9 publications

References 30 publications

SMAD4–201 transcript as a putative biomarker in colorectal cancer

SMAD4–201 transcript as a putative biomarker in colorectal cancer

Reciprocal Dysregulation of MiR-146b and MiR-451 Contributes in Malignant Phenotype of Follicular Thyroid Tumor

A narrative review of the relationship between TGF-β signaling and gynecological malignant tumor

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