TCF19 Enhances Glioma Cell Proliferation via Modulating the Β-Catenin Signaling Pathway through Accelerating DHX32 Transcription.

IF 2.3 4区 医学 Q3 ONCOLOGY Current cancer drug targets Pub Date : 2025-01-20 DOI:10.2174/0115680096360071241215171342
Jing Tan, Haiping Lian, Qi Zheng, Tingting Yang, Tuo Wang
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Abstract

Background: Transcription factor 19 (TCF19) is considered a crucial transcription factor and acts as an oncogene in a few cancers. Nevertheless, the effect and mechanism of TCF19 on glioma remain unknown.

Objective: This research aimed to explore the function of TCF19 on glioma progression and clarify the potential mechanism.

Methods: TCF19 and DHX32 expressions in glioma were determined using bioinformatics, Quantitative real-time PCR, and immunohistochemistry. MTT assay was carried out to detect the biological function of TCF19 and DHX32 in glioma cell multiplication. Cell-cycle distri-bution and apoptosis were measured by using FACS. The function of TCF19 on glioma growth was examined using tumor xenografts assay. Bioinformatics analysis, ChIP-qRT-PCR, and reporter gene assay were employed to illustrate the TCF19 target regulating DHX32 tran-scription.

Results: TCF19 was observably upregulated in glioma and has important clinical significance. Overexpressing TCF19 expedited glioma cell multiplication and cell-cycle transition, mean-while preventing apoptosis. TCF19 knockdown inhibited cell proliferation, cell-cycle transi-tion, and tumour growth, simultaneously accelerating apoptosis. TCF19 expressions had a positive correlation with DHX32 expressions in glioma. It was demonstrated that TCF19 acti-vated DHX32 transcriptional activity in glioma by combining it with the promoter of DHX32. DHX32 promoted glioma cell growth and cell-cycle transition while restraining apoptosis. Overexpressing DHX32 eliminated the function of TCF19 knockdown on cell multiplication, cell-cycle transition, and apoptosis. Moreover, TCF19 activated the β-catenin pathway by en-hancing DHX32 transcriptional activity.

Conclusion: TCF19 promotes glioma cell multiplication and cell-cycle transition while sup-pressing apoptosis by modulating the β-catenin signaling pathway via accelerating DHX32 transcription. These findings provide a promising therapeutic target for glioma.

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TCF19通过加速DHX32转录调控Β-Catenin信号通路促进胶质瘤细胞增殖
背景:转录因子19 (Transcription factor 19, TCF19)被认为是一种重要的转录因子,在一些癌症中起致癌基因的作用。然而,TCF19在胶质瘤中的作用和机制尚不清楚。目的:本研究旨在探讨TCF19在胶质瘤进展中的作用并阐明其潜在机制。方法:采用生物信息学、实时荧光定量PCR和免疫组织化学检测胶质瘤组织中TCF19和DHX32的表达。MTT法检测TCF19和DHX32在胶质瘤细胞增殖中的生物学功能。流式细胞仪检测细胞周期分布及凋亡情况。采用肿瘤异种移植实验检测TCF19对胶质瘤生长的作用。采用生物信息学分析、ChIP-qRT-PCR和报告基因检测等方法分析TCF19调控DHX32转录的靶点。结果:TCF19在胶质瘤中表达明显上调,具有重要的临床意义。过表达TCF19促进胶质瘤细胞增殖和细胞周期转变,同时阻止细胞凋亡。TCF19敲低抑制细胞增殖、细胞周期转变和肿瘤生长,同时加速细胞凋亡。胶质瘤中TCF19表达与DHX32表达呈正相关。结果表明,TCF19通过与DHX32启动子结合,激活了胶质瘤中DHX32的转录活性。DHX32促进胶质瘤细胞生长和细胞周期转变,抑制细胞凋亡。过表达DHX32消除了TCF19敲除对细胞增殖、细胞周期转变和细胞凋亡的作用。此外,TCF19通过增强DHX32的转录活性来激活β-catenin通路。结论:TCF19通过加速DHX32转录,调控β-catenin信号通路,促进胶质瘤细胞增殖和细胞周期转变,同时抑制细胞凋亡。这些发现为胶质瘤提供了一个有希望的治疗靶点。
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来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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