ZBTB 7A调控LncRNA HOTAIR介导的ELAVL 1/SOX 17轴抑制子宫内膜癌恶性程度和血管生成

ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma            

ZBTB 7A调控LncRNA HOTAIR介导的ELAVL 1/SOX 17轴抑制子宫内膜癌恶性程度和血管生成

Authors: Zhang XH, Wu SW, Feng YF, Xie YQ, Li M, Hu P, Cao Y.

Source：J Cancer Res Clin Oncol. 2024 Jul 9;150(7):345. doi: 10.1007/s00432-024-05860-w.

Abstract

Background: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.

Methods: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.

Results: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.

Conclusion: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.

Keywords: Endometrial carcinoma; HOTAIR; SOX17; Wnt-β-catenin pathway; ZBTB7A.

摘要

背景：子宫内膜癌（EC）是世界范围内第六大常见的女性癌症，具有较高的病死率。EC的病理生理学是复杂的，并且目前没有用于诊断和治疗该病症的可靠方法。越来越多的证据表明，长链非编码RNA（lncRNA）在EC的病理生理过程中起着重要作用。HOTAIR被认为是EC的重要预后指标。最近的研究表明，ZBTB7A可抑制EC的增殖和迁移，但其潜在机制仍需阐明。

方法：采用RT-qPCR方法检测HOTAIR在临床食管癌组织和各种食管癌细胞系中的表达。采用Kaplan-Meier生存分析将HOTAIR水平与患者预后相关联。此外，该研究还使用生物信息学工具和ChIP测定法检查了ZBTB 7A和HOTAIR之间的相互作用。实验方法还涉及操纵EC细胞系中HOTAIR和ZBTB 7A的表达水平，并评估对各种细胞过程和基因表达的影响。

结果如下：该研究发现，与邻近的正常组织相比，EC组织中的HOTAIR水平显著较高，HOTAIR高表达与较差的生存率和晚期癌症特征相关。EC细胞系如HEC-1A和KLE与正常细胞相比显示出更高的HOTAIR水平。在这些细胞系中HOTAIR的敲低降低了增殖、血管生成和迁移。研究发现ZBTB 7A与HOTAIR呈负相关，其过表达导致HOTAIR水平降低和恶性细胞行为减少。该研究还发现HOTAIR与ELAVL 1相互作用以调节SOX 17，SOX 17反过来激活Wnt/β-catenin通路，促进EC细胞的恶性行为。

结论：HOTAIR是EC中的关键调节剂，有助于肿瘤生长和不良预后。其与ZBTB 7A的相互作用以及通过Wnt/β-连环蛋白途径调节S 0X 17强调了其作为治疗靶标的潜力。

关键词：子宫内膜癌; HOTAIR; SOX 17; Wnt-β-catenin通路; ZBTB 7A.