E2F8-TPX2 轴调节糖酵解和血管生成,促进肝癌的进展并降低其化疗敏感性。

IF 2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Cytotechnology Pub Date : 2024-12-01 Epub Date: 2024-09-21 DOI:10.1007/s10616-024-00655-w
Xiao-Qing Li, Zhen-Rui Cao, Min Deng, Yun Qing, Lan Sun, Zhong-Jun Wu
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引用次数: 0

摘要

肝癌(LC)是全球关注的健康问题,其发病率和死亡率都很高,并以对化疗的耐药性而闻名。肝癌患者的治疗面临着巨大挑战。爪蟾驱动蛋白样蛋白 2(TPX2)靶向蛋白是近年来发现的一种肝癌标志物,有零星数据表明它对化疗耐药水平有影响,但其确切机制仍有待破解。我们的研究以生物信息学策略为基础,包括TCGA数据库、GEO数据库、K-M图数据库、GSEA、Pearson相关性分析和临床样本检测,最终确定了TPX2及其上游转录因子E2F8在LC组织中的差异表达。我们还探究了该轴在 LC 细胞的糖酵解、血管生成、肿瘤进展和化疗抗性中的作用。为此,我们进行了一系列分子和细胞实验,如 qRT-PCR、CCK-8、Transwell、流式细胞术和血管生成实验。TPX2和E2F8都在LC组织和细胞中上调,其中E2F8是TPX2上调的原因。通过生物信息学分析,我们观察到 TPX2 在糖酵解和血管生成通路中显著富集。基于细胞的实验证实了这些发现,表明敲除 TPX2 会显著抑制糖酵解和血管生成,同时抑制 LC 细胞的恶性发展。顺铂和阿帕替尼的 IC50 值分别降至 0.8257 µM 和 10.79 µM,也反映了这一点。与此相反,E2F8 的过表达逆转了 LC 细胞中的这些效应,使 IC50 值分别增加到 3.375 µM 和 16.06 µM。E2F8-TPX2轴促进LC细胞中的糖酵解和血管生成,进而加速癌症进展并降低化疗敏感性:在线版本包含补充材料,见 10.1007/s10616-024-00655-w。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
E2F8-TPX2 axis regulates glycolysis and angiogenesis to promote progression and reduce chemosensitivity of liver cancer.

Liver cancer (LC) is a global health concern, marked by its high prevalence and mortality rates and known for its resistance to chemotherapy. The treatment of LC patients is facing great challenges. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a LC marker that has been discovered in recent years, and there are sporadic data suggesting that it has an impact on the level of chemoresistance, but the exact mechanism remains to be deciphered. Our investigation, grounded in bioinformatics strategies including the TCGA database, GEO database, K-M plot database, GSEA, Pearson correlation analysis, and detection of clinical samples, led to the identification of TPX2 and its upstream transcription factor E2F8 as differentially expressed elements in LC tissues. We also probed the role of the axis in glycolysis, angiogenesis, tumor progression, and chemoresistance in LC cells. This was achieved by a battery of molecular and cellular experiments, such as qRT-PCR, CCK-8, Transwell, flow cytometry, and angiogenesis assays. Both TPX2 and E2F8 were upregulated in LC tissues and cells with E2F8 being responsible for the upregulation of TPX2. Through bioinformatics analysis, we observed a significant enrichment of TPX2 in the glycolysis and angiogenesis pathways. Cell-based experiments corroborated these findings, demonstrating that TPX2 knockdown led to significant inhibition of glycolysis and angiogenesis, along with a suppression of the malignant progression of LC cells. This was mirrored by a reduction in the IC50 values for cisplatin and apatinib to 0.8257 µM and 10.79 µM, respectively. In contrast, E2F8 overexpression reversed these effects in LC cells, increasing the IC50 values to 3.375 and 16.06 µM, respectively. The E2F8-TPX2 axis promotes glycolysis and angiogenesis in LC cells, which in turn accelerates cancer progression and reduces chemosensitivity.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-024-00655-w.

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来源期刊
Cytotechnology
Cytotechnology 生物-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
49
审稿时长
6-12 weeks
期刊介绍: The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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