lncRNA799/TBL1XR1/ZEB1 Axis Forms a Feedback Loop to Promote the Epithelial-Mesenchymal Transition of Cervical Cancer Cells.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2023049916
Lingmin Liao, Peng Huang, Jiali Zhao, Ziying Wang, He Chen, Chunquan Zhang, Long Huang
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Abstract

Cervical cancer is a common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) are frequently involved in the pathogenesis of cervical cancer. Therefore, the present study aimed to investigate the potentials of lncRNA799 in cervical cancer. mRNA and protein expression were detected by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. Cellular functions were assessed using CCK-8, wound healing and transwell analysis. The binding potential of zinc finger E-box-binding homeobox 1 (ZEB1) on the promoter of lncRNA799 was predicted utilizing the JASPAR database, and was then verified by luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, the gene interactions were assessed using RNA immunoprecipitation and co-immunoprecipitation assays. The results demonstrated that lncRNA799 was upregulated in cervical cancer cells. However, lncRNA799 deficiency suppressed the proliferation and epithelial-mesenchymal transition of cervical cancer cells. Furthermore, lncRNA799 could interact with eukaryotic translation initiation factor 4A3 to maintain the mRNA stability of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) and promote the interaction between ZEB1 and TBL1XR1. Additionally, the results showed that ZEB1 could transcriptionally activate lncRNA799. Taken together, the present study suggested that the lncRNA799/TBL1XR1/ZEB1 axis could form a positive feedback loop in cervical cancer and could be, therefore, considered as a potential therapeutic strategy for cervical cancer.

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lncRNA799/TBL1XR1/ZEB1轴形成促进宫颈癌细胞上皮-间充质转化的反馈回路
宫颈癌是全球妇女常见的恶性肿瘤。长非编码 RNA(lncRNA)经常参与宫颈癌的发病机制。因此,本研究旨在探讨 lncRNA799 在宫颈癌中的潜在作用。mRNA 和蛋白质表达分别通过逆转录-定量聚合酶链反应和 Western 印迹分析进行检测。利用CCK-8、伤口愈合和透孔分析评估了细胞功能。利用 JASPAR 数据库预测了锌指 E-box-binding homeobox 1(ZEB1)在 lncRNA799 启动子上的结合潜力,并通过荧光素酶和染色质免疫沉淀(ChIP)实验进行了验证。此外,还利用 RNA 免疫沉淀和共免疫沉淀试验评估了基因之间的相互作用。结果表明,lncRNA799在宫颈癌细胞中上调。然而,缺乏lncRNA799会抑制宫颈癌细胞的增殖和上皮-间质转化。此外,lncRNA799可与真核翻译起始因子4A3相互作用,维持转导蛋白(β)样1 X连锁受体1(TBL1XR1)的mRNA稳定性,并促进ZEB1与TBL1XR1之间的相互作用。此外,研究结果表明,ZEB1 可转录激活 lncRNA799。综上所述,本研究表明,lncRNA799/TBL1XR1/ZEB1轴可在宫颈癌中形成正反馈环,因此可被视为宫颈癌的一种潜在治疗策略。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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