Dataset Information

Contribution of TWIST1-EVX1 Axis in Invasiveness of Esophageal Squamous Cell Carcinoma; a Functional Study.

ABSTRACT:

Background

Epithelial-mesenchymal transition (EMT) is a biological process in embryonic development and cancer progression, and different gene families, such as HOX genes, are closely related to this process.

Objectives

Our aim in this study was to investigate the correlation between TWIST1 and EVX1 mRNA expression in ESCC patients and also examine the probable regulatory function of TWIST1 on EVX1 expression in human ESCC cell line.

Materials and methods

TWIST1 and EVX1 gene expression patterns were assessed in ESCC patients by relative comparative Real-time PCR then correlated with their clinical characteristics. In silico analysis of the EVX1 gene was conducted. KYSE-30 cells were transduced by a retroviral system to ectopically express TWIST1, followed by qRT-PCR to reveal the correlation between TWIST1 and EVX1 gene expression.

Results

The expression of TWIST1 and EVX1 was correlated to each other significantly (p=0.005) in ESCC. Of 28 patients with under/normal expression of TWIST1, 22 samples (78.57%) had over/normal expression of EVX1. TWIST1 overexpression was correlated with advanced stages of the tumor (III, IV) (P = 0.019) and lymph node metastasis. However, EVX1 under expression was associated with lymph node metastasis (p = 0.027) and invasiveness of the disease (P = 0.037) in ESCC. Furthermore, retroviral transduction enforced significant overexpression of TWIST1 in GFP-hTWIST-1 approximately 9-fold compared to GFP control cells, causing a - 8.83- fold reduction in EVX1 mRNA expression significantly.

Conclusions

Our results indicated the repressive role of TWIST1 on EVX1 gene expression in ESCC. Therefore, our findings can help dissect the molecular mechanism of ESCC tumorigenesis and discover novel therapeutic targets for ESCC invasion and metastasis.

SUBMITTER: Ardalan Khales S

PROVIDER: S-EPMC9583822 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Contribution of TWIST1-EVX1 Axis in Invasiveness of Esophageal Squamous Cell Carcinoma; a Functional Study.

Ardalan Khales Sepideh S Abbaszadegan Mohammad Reza MR Hosseini Seyed Ebrahim SE Forghanifard Mohammad Mahdi MM

Iranian journal of biotechnology 20220401 2

<h4>Background</h4>Epithelial-mesenchymal transition (EMT) is a biological process in embryonic development and cancer progression, and different gene families, such as HOX genes, are closely related to this process.<h4>Objectives</h4>Our aim in this study was to investigate the correlation between TWIST1 and EVX1 mRNA expression in ESCC patients and also examine the probable regulatory function of TWIST1 on EVX1 expression in human ESCC cell line.<h4>Materials and methods</h4>TWIST1 and EVX1 ge ...[more]

PMID: 36337061

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Project description:Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial-mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3'-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.

Dataset Information

Contribution of TWIST1-EVX1 Axis in Invasiveness of Esophageal Squamous Cell Carcinoma; a Functional Study.

Background

Objectives

Materials and methods

Results

Conclusions

Publications

Contribution of TWIST1-EVX1 Axis in Invasiveness of Esophageal Squamous Cell Carcinoma; a Functional Study.

Similar Datasets

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