Impact and mechanism of the TBX-22 gene mutation G874A on the epithelial-mesenchymal transition in medial edge epithelial cells.

IF 1.5 4区 生物学 Q4 CELL BIOLOGY
Chen Xu, Yali Hou, Li Ma, Dongsheng Zhang
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引用次数: 0

Abstract

Cleft lip and palate (CL/P) are prevalent congenital anomalies with complex genetic causes. The G874A mutation of T-box transcription factor 22 (TBX-22) gene is notably associated with CL/P, while the underlying mechanism remains to be clarified. Studies have shown that the restriction of epithelial-mesenchymal transformation (EMT) process in medial edge epithelial cells (MEEs) is crucial for CL/P development. In our current research, primary MEEs, isolated and cultured from mouse embryos, were genetically introduced the TBX-22 G874A mutation and subsequently treated with TGF-β1. They were then utilized to test the hypothesis that the G874A mutation in TBX22 plays a role in the regulation of the EMT in MEEs. Our findings reveal that TBX22 reduces miR140-5p transcription by binding to its promoter, while miR140-5p downregulates TGFBR1 protein expression by targeting its mRNA 3'-UTR. In other words, TBX22 could indirectly positively regulates TGFBR1 expression post-transcriptionally. Functional cellular assays showed that the G874A mutation of TBX-22 counteracted TGF-β1-induced decrease in proliferation and migration. Western blotting results showed that the G874A mutation of TBX-22 inhibited EMT protein expression (α-SMA and Vimentin) and promoted E-cadherin in TGF-β1-induced MEEs. To summarize, our research reveals that the G874A mutation of TBX22 impedes the progression of EMT in MEEs through the upregulation of miR140-5p and the downregulation of TGFBR1. This highlights TGFBR1 as a viable target for the prevention of CL/P.

TBX-22基因突变G874A对内边缘上皮细胞上皮-间质转化的影响及机制
唇腭裂是一种常见的先天性畸形,具有复杂的遗传原因。T-box转录因子22 (T-box transcription factor 22, tx -22)基因G874A突变与CL/P显著相关,但其机制尚不清楚。研究表明,限制内边缘上皮细胞(MEEs)的上皮-间充质转化(EMT)过程对CL/P的发展至关重要。在我们目前的研究中,从小鼠胚胎中分离和培养原代MEEs,遗传引入TBX-22 G874A突变,随后用TGF-β1处理。然后利用它们来验证TBX22中的G874A突变在MEEs的EMT调控中起作用的假设。我们的研究结果表明TBX22通过结合其启动子来降低miR140-5p的转录,而miR140-5p通过靶向其mRNA 3'-UTR来下调TGFBR1蛋白的表达。也就是说,TBX22可以间接正调控TGFBR1转录后的表达。功能细胞实验显示,TBX-22的G874A突变抵消了TGF-β1诱导的增殖和迁移的减少。Western blotting结果显示,TBX-22基因G874A突变抑制TGF-β1诱导的MEEs中EMT蛋白(α-SMA和Vimentin)的表达,促进E-cadherin的表达。综上所述,我们的研究表明TBX22的G874A突变通过上调miR140-5p和下调TGFBR1来阻碍MEEs中EMT的进展。这表明TGFBR1是预防CL/P的可行靶点。
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来源期刊
CiteScore
3.70
自引率
4.80%
发文量
96
审稿时长
3 months
期刊介绍: In Vitro Cellular & Developmental Biology - Animal is a journal of the Society for In Vitro Biology (SIVB). Original manuscripts reporting results of research in cellular, molecular, and developmental biology that employ or are relevant to organs, tissue, tumors, and cells in vitro will be considered for publication. Topics covered include: Biotechnology; Cell and Tissue Models; Cell Growth/Differentiation/Apoptosis; Cellular Pathology/Virology; Cytokines/Growth Factors/Adhesion Factors; Establishment of Cell Lines; Signal Transduction; Stem Cells; Toxicology/Chemical Carcinogenesis; Product Applications.
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