Long non-coding RNA HOTAIR promotes tumorigenesis by affecting proliferation, invasion, migration and apoptosis of liver cancer cells.

IF 1.7 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Folia histochemica et cytobiologica Pub Date : 2024-11-26 DOI:10.5603/fhc.100686

Xinzi Zheng, Renyin Cui, Yan Jiao, Dongxia Chu, Bingrong Wang, Na Li

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引用次数: 0

Abstract

Introduction: Increasing evidence shows that Hox transcript antisense RNA (HOTAIR) plays a vital role in liver cancer initiation and progression by affecting the proliferation, invasion, migration and apoptosis of liver cancer cells. However, the underlying mechanism of how HOTAIR exerts its functions in liver cancer cells remains unclear. Previous studies have shown that HOTAIR affects the invasion and migration of liver cancer cells by regulating the expression of E-cadherin. Snail2, a transcription factor involved in epithelial-mesenchymal transition, directly binds to the E-boxes of theE-cadherinpromoter to repress its transcription. The aim of the study was to examine the correlation between HOTAIR and Snail2 in the HOTAIR/Snail2/E-cadherin signal pathway and explore the role of HOTAIR in the proliferation, invasion, migration and apoptosis of liver cancer cells.

Materials and methods: 50 matched normal liver tissues and 373 liver cancer tissues were analysed and evaluated. HepG2 and SNU-387 cells were cultured and transfected with plasmids knocking down HOTAIR to disrupt HOTAIR expression. Cell scratch and transwell assays were performed to examine the migration and invasion of HepG2 and SNU-387 cells; in addition, the expression of MMP2 and MMP9 was detected by immunoblotting analysis, RT-qPCR analysis, immunofluorescence analysis, and bioinformatics analysis, which elucidated the regulatory relationship between HOTAIR and Snail2. We used flow cytometry and JC-1 probe analysis assays to clarify the function of HOTAIR in liver cancer cell apoptosis.

Results: The HOTAIR mRNA was upregulated in liver cancer tissues, which was related to worse overall survival. HOTAIR induced the expression of matrix metalloproteinase-9 (MMP9) and metalloproteinase-2 (MMP2), leading to degradation of extracellular matrix. HOTAIR knockdown significantly reduced the doubling time and inhibited cell migration and invasion of liver cancer cells. Furthermore, HOTAIR depletion induced mitochondrial-related apoptosis in HepG2 and SNU-387 cell lines.

Conclusions: In this study, we proposed a novel mechanism in which HOTAIR promotes invasion and migration of liver cancer cells by regulating the nuclear localization of Snail2.

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长非编码 RNA HOTAIR 通过影响肝癌细胞的增殖、侵袭、迁移和凋亡，促进肿瘤发生。

导言：越来越多的证据表明，Hox 转录本反义 RNA（HOTAIR）通过影响肝癌细胞的增殖、侵袭、迁移和凋亡，在肝癌的发生和发展过程中发挥着至关重要的作用。然而，HOTAIR如何在肝癌细胞中发挥其功能的内在机制仍不清楚。先前的研究表明，HOTAIR 通过调节 E-cadherin 的表达影响肝癌细胞的侵袭和迁移。参与上皮-间质转化的转录因子 Snail2 可直接与 E-cadherin 启动子的 E-boxes 结合，抑制其转录。本研究旨在研究 HOTAIR 和 Snail2 在 HOTAIR/Snail2/E-cadherin 信号通路中的相关性，并探讨 HOTAIR 在肝癌细胞增殖、侵袭、迁移和凋亡中的作用。培养 HepG2 和 SNU-387 细胞并转染敲除 HOTAIR 的质粒以破坏 HOTAIR 的表达。此外，我们还通过免疫印迹分析、RT-qPCR分析、免疫荧光分析和生物信息学分析检测了MMP2和MMP9的表达，从而阐明了HOTAIR和Snail2之间的调控关系。我们利用流式细胞术和JC-1探针分析法明确了HOTAIR在肝癌细胞凋亡中的功能：结果：HOTAIR mRNA在肝癌组织中上调，这与总生存率的下降有关。HOTAIR诱导基质金属蛋白酶-9（MMP9）和金属蛋白酶-2（MMP2）的表达，导致细胞外基质降解。敲除 HOTAIR 能显著缩短肝癌细胞的倍增时间，抑制细胞迁移和侵袭。此外，HOTAIR 缺失还诱导了 HepG2 和 SNU-387 细胞系中线粒体相关的细胞凋亡：本研究提出了一种新的机制，即 HOTAIR 通过调节 Snail2 的核定位促进肝癌细胞的侵袭和迁移。

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来源期刊

Folia histochemica et cytobiologica 生物-生化与分子生物学

CiteScore

2.80

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.