Silencing SIX1 inhibits epithelial mesenchymal transition through regulating TGF-β/Smad2/3 signaling pathway in papillary thyroid carcinoma

Min, Wen-Pu; Wei, Xiaofeng

doi:10.1016/j.anl.2020.10.002

Cited by 16 publications

(16 citation statements)

References 38 publications

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“…TNF-a, a proinflammatory cytokine, enhances TGF-b-induced EMT by activating the Smad2/3 signal (44). A similar mechanism is found for SIX1 in papillary thyroid carcinoma (45). Further, SIX1 increases CSC recruit macrophages and stimulate angiogenesis, contributing to the progression of cancer.…”

Section: Discussionsupporting

confidence: 65%

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

et al. 2022

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BackgroundsEpithelial–mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC).MethodsEMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs.ResultsA total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher N6-methyladenosine (m6A) RNA expression, microsatellite instability level, and stemness indices.ConclusionWe constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.

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Section: Discussionsupporting

confidence: 65%

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

et al. 2022

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“…It has been found that thyroid cancers with lymphatic metastasis are more likely to have Ecadherin methylation and low expression of E-cadherin [ 13 ]. Thyroid tumors are divided into benign tumor, differentiated thyroid carcinoma, poorly differentiated thyroid carcinoma and undifferentiated thyroid carcinoma according to the pathological types [ 62 ]. With the increase of malignant degree, the positive expression rate of E-cadherin decreases gradually, which is negatively correlated with higher clinical stage, distant lymph node metastasis, extracapsular infiltration and lower disease-free survival rate [ 62 , 173 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid tumors are divided into benign tumor, differentiated thyroid carcinoma, poorly differentiated thyroid carcinoma and undifferentiated thyroid carcinoma according to the pathological types [ 62 ]. With the increase of malignant degree, the positive expression rate of E-cadherin decreases gradually, which is negatively correlated with higher clinical stage, distant lymph node metastasis, extracapsular infiltration and lower disease-free survival rate [ 62 , 173 ]. And in gastric cancer, breast cancer, ovarian cancer and other tumors also showed that the low expression of E-cadherin-induced EMT is related to the invasive characteristics of tumors, and become an independent prognostic factor of tumor patients [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, an experiment showed that by down-regulating Smurf, the ubiquitin ligase of Smad3, the TFG-β/SMAD pathway could be affected, thus down-regulating the expression of EMT marker E-cadherin in thyroid cancer [ 61 ]. Another study found that E-cadherin was inhibited by affecting the expression of TGF-β/Smad2/3 pathway [ 62 , 63 ]. It may be related to the regulation of the transcription factor Snail and the tumor suppressor gene BRAFV600E.…”

Section: Signaling Pathway Of Regulating E-cadherinmentioning

confidence: 99%

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E-cadherin on epithelial–mesenchymal transition in thyroid cancer

et al. 2021

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Thyroid carcinoma is a common malignant tumor of endocrine system and head and neck. Recurrence, metastasis and high malignant expression after routine treatment are serious clinical problems, so it is of great significance to explore its mechanism and find action targets. Epithelial–mesenchymal transition (EMT) is associated with tumor malignancy and invasion. One key change in tumour EMT is low expression of E-cadherin. Therefore, this article reviews the expression of E-cadherin in thyroid cancers (TC), discuss the potential mechanisms involved, and outline opportunities to exploit E-cadherin on regulating the occurrence of EMT as a critical factor in cancer therapeutics.

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“…SIX1 induces EMT by activating TGFβ or ZEB1 signaling 39–41 . SIX1 depletion suppresses EMT via repressing the TGFβ signaling pathway and reversed SIX1 re‐induces TGFβ signaling 42–44 . The KLF family plays a critical role in tumor development and is reported to be associated with EMT 45 .…”

Section: The Pivotal Roles Of Transcriptional Regulation In Cancer De...mentioning

confidence: 99%

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

Pei

Guo

Peng

et al. 2022

Medicinal Research Reviews

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The key proteins involved in transcriptional regulation play convergent roles in cellular homeostasis, and their dysfunction mediates aberrant gene expressions that underline the hallmarks of tumorigenesis. As tumor progression is dependent on such abnormal regulation of transcription, it is important to discover novel chemical entities as antitumor drugs that target key tumor‐associated proteins involved in transcriptional regulation. Despite most key proteins (especially transcription factors) involved in transcriptional regulation are historically recognized as undruggable targets, multiple targeting approaches at diverse levels of transcriptional regulation, such as epigenetic intervention, inhibition of DNA‐binding of transcriptional factors, and inhibition of the protein–protein interactions (PPIs), have been established in preclinically or clinically studies. In addition, several new approaches have recently been described, such as targeting proteasomal degradation and eliciting synthetic lethality. This review will emphasize on accentuating these developing therapeutic approaches and provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.

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Silencing SIX1 inhibits epithelial mesenchymal transition through regulating TGF-β/Smad2/3 signaling pathway in papillary thyroid carcinoma

Cited by 16 publications

References 38 publications

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

E-cadherin on epithelial–mesenchymal transition in thyroid cancer

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

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