TGF-β1 functional polymorphisms: a review

Cebinelli, Guilherme Cesar Martelossi; Trugilo, Kleber Paiva; Garcia, Stephanie Badaró; Oliveira, Karen Brajão de

doi:10.1684/ecn.2016.0382

Cited by 84 publications

(60 citation statements)

References 98 publications

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“…This SNP (Single Nucleotide Polymorphism) is located in a region encoding the hydrophobic core of the TGF-β1 signal peptide and results in a substitution of proline with leucine in the 10th position of the amino acid sequence. The c.+29C results in increased TGF-β1 secretion in vitro and in vivo compared with c.+29T [178]. Chen et al found Int7G24A (rs334354) intronic variant of the TGFBR1 gene frequently associates with transitional cell carcinoma (TCC) of the bladder as well as renal cell carcinoma [141].…”

Section: Bladder Cancermentioning

confidence: 99%

“…Specifically, homozygotic TT patients had a lower risk of recurrence following BCG treatment [341]. Interestingly, this genotype is associated with increased TGF-β expression when compared with CC homozygotes, and individuals with T substitution have twice higher TGF-β1 plasma concentrations when compared with CC carriers [174,178]. TGF-β modulates the functioning of myeloid-derived suppressor cells (MDSCs) of bladder cancer patients.…”

Section: Tgf-β1 and Micrornas And Treatment Of Gcmentioning

confidence: 99%

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TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

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Section: Bladder Cancermentioning

confidence: 99%

Section: Tgf-β1 and Micrornas And Treatment Of Gcmentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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“…Both tumorigenic and tumor-suppressive roles of TGF-β1 have been well established [5]. Elevated plasma levels of TGF-β1 have been associated with cancer development, and TGF-β1 polymorphisms have been found to cause high transcription and expression of TGF-β1 [9,11]. The prominent role of TGF-β1 in cancer progression underscores the importance of studying the association between TGF-β1 polymorphisms and BC risk.…”

Section: Discussionmentioning

confidence: 99%

“…Several polymorphisms have been identified in the TGF-β1 gene (TGFβ1), including two located in exon 1 (TGF-β1 29T>C and TGF-β1*6A) and two located in the promoter region (TGF-β1-509 C/T and TGF-β1-800 G/A) [8][9][10]. There is increasing evidence of an association between these polymorphisms and elevated cancer risk [11]. Researchers demonstrated that the TGF-β1 29T>C polymorphism increases the secretion of TGF-β levels [9].…”

Section: Introductionmentioning

confidence: 99%

Association of TGF-β1 Polymorphisms with Breast Cancer Risk: A Meta-Analysis of Case–Control Studies

Krishna

Jana

Panda³

et al. 2020

Cancers

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Reports on the association of TGF-β1 polymorphisms with breast cancer (BC) have been conflicting, inconsistent, inconclusive, and controversial. PubMed, EMBASE, and Google Scholar were used to identify studies on TGF-β1 polymorphisms and BC risk. Data were extracted independently, and of the initial 3043 studies, 39 case-control studies were eligible for inclusion in the meta-analysis. Information from these studies was extracted, and the overall associations of three TGF-β1 polymorphisms (TGF-β1 29>T/C, TGF-β1-509 C/T, and TGF-β1*6A) with BC risk were analyzed using overall allele, homozygous, heterozygous, recessive, and dominant models. None of the three TGF-β1 polymorphisms studied had a significant influence on the development of BC. However, stratified analysis revealed a positive correlation between the TGF-β1 29T>C polymorphism and BC risk according to a heterozygous model of the Asian population (odds ratio (OR) = 1.115, 95% confidence interval (CI) = 1.006–1.237, p = 0.039). Interestingly, this polymorphism was associated with lower odds of BC according to a heterozygous model of the Middle Eastern population (OR = 0.602, 95% CI = 0.375–0.966, p = 0.035). Thus, our analysis of large datasets indicates that the TGF-β1 29T>C polymorphism is significantly associated with BC risk in the Asian population. In contrast, the TGF-β1*6A and TGF-β1-509 C/T polymorphisms failed to show an association with BC.

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“…Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates cell growth and differentiation, as well as regulates cell proliferation through the TGF-β/Smad signaling pathway (Martelossi Cebinelli, Paiva, Badaró, et al, 2016). TGF-β/Smad signaling dysregulation has been frequently observed in various types of cancers (Kaminska, Wesolowska, & Danilkiewicz, 2016).…”

mentioning

confidence: 99%

Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF‐β/Smad signaling pathway

Zhao

Wang

et al. 2018

Dermatologic Therapy

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Objective To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV. Methods MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins. Results AS‐IV reduced the proliferation of SW962 cells in a concentration‐ and time‐dependent manner, induced cell‐cycle arresting in G0/G1 phase, as demonstrated by the up‐regulation of P53 and P21 expression, and the down‐regulation of cyclin D1 expression. AS‐IV enhanced the expression of Bax and cleaved‐caspase 3, and suppressed Bcl‐2 and Bcl‐xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin‐1 and LC3‐B was upregulated and that of P62 was downregulated, which suggested that AS‐IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3‐methyladenine (3‐MA), cell apoptosis decreased upon AS‐IV treatment. Similarly, TGF‐β1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF‐βRII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS‐IV treatment, the expression levels of the above proteins exhibited the opposite effect. Conclusion AS‐IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF‐β/Smad signaling pathway in VSCC.

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TGF-β1 functional polymorphisms: a review

Cited by 84 publications

References 98 publications

TGF-β and microRNA Interplay in Genitourinary Cancers

TGF-β and microRNA Interplay in Genitourinary Cancers

Association of TGF-β1 Polymorphisms with Breast Cancer Risk: A Meta-Analysis of Case–Control Studies

Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF‐β/Smad signaling pathway

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