circHMGCS1通过调节HuR/SFPQ/TNF通路促进NSCLC的进展

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jiayue An, Weimiao Sun, Chenhui Ti, Yulong Mu, Baohui Yin, Qin Wang, Xia Zhang, Yan Liang, Hongfang Sun, Shuyang Xie, Youjie Li
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引用次数: 0

摘要

在肺癌中,非小细胞肺癌(NSCLC)是最常见的类型。有证据表明,环状rna (circRNAs)的异常表达通过与rna结合蛋白(rbp)的相互作用与癌症进展相关。因此,进一步阐明环状rna的作用可能为NSCLC患者提供新的治疗靶点。本研究使用circRNA微阵列鉴定了一种新的circHMGCS1 (hsa_circ_0072387)。通过Sanger测序和RNase R处理对circHMGCS1进行验证和表征。CCK-8和Transwell检测circHMGCS1在细胞增殖和迁移中的功能。circHMGCS1与人抗原R (HuR)蛋白的相互作用通过RNA pull-down和RNA免疫沉淀(RIP)验证。通过双荧光素酶报告基因检测和放线菌素D处理验证了HuR对富含脯氨酸和谷氨酰胺剪接因子(SFPQ) mRNA稳定性的影响。我们发现circHMGCS1在NSCLC细胞和组织中表达上调。从机制上讲,circHMGCS1与HuR结合,其高表达通过抑制其泛素介导的降解来稳定HuR。研究表明,HuR介导SFPQ mRNA的稳定性,促进NSCLC的进展。RNA测序分析表明SFPQ可能通过抑制肿瘤坏死因子(TNF)信号传导抑制细胞凋亡。本研究表明,circHMGCS1通过稳定致癌HuR和促进SFPQ转录后上调来促进非小细胞肺癌的进展,突出了其作为非小细胞肺癌诊断和预后生物标志物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

circHMGCS1 Promotes the Progression of NSCLC by Regulating the HuR/SFPQ/TNF Pathway

circHMGCS1 Promotes the Progression of NSCLC by Regulating the HuR/SFPQ/TNF Pathway

circHMGCS1 Promotes the Progression of NSCLC by Regulating the HuR/SFPQ/TNF Pathway

circHMGCS1 Promotes the Progression of NSCLC by Regulating the HuR/SFPQ/TNF Pathway

Among lung cancers, non-small-cell lung cancer (NSCLC) is the most common type. Evidence demonstrates that abnormal expression of circular RNAs (circRNAs) is associated with cancer progression through interactions with RNA-binding proteins (RBPs). Therefore, further elucidation of the role of circular RNAs may provide new therapeutic targets for NSCLC patients. This study identified a novel circRNA, circHMGCS1 (hsa_circ_0072387), using circRNA microarrays. Validation and characterization of circHMGCS1 were performed by Sanger sequencing and RNase R treatment. CCK-8 and Transwell assays were used to determine the function of circHMGCS1 in cell proliferation and migration. The interaction between circHMGCS1 and human antigen R (HuR) protein was verified by RNA pull-down and RNA immunoprecipitation (RIP) assays. The effect of HuR on the stability of splicing factor proline- and glutamine-rich (SFPQ) mRNA was verified by dual-luciferase reporter gene assay and actinomycin D treatment. We found that circHMGCS1 was upregulated in NSCLC cells and tissues. Mechanistically, circHMGCS1 binds to HuR, and its high expression stabilizes HuR by inhibiting its ubiquitin-mediated degradation. HuR was shown to mediate the stability of SFPQ mRNA and promote the progression of NSCLC. RNA sequencing analysis indicated that SFPQ may inhibit apoptosis by suppressing tumor necrosis factor (TNF) signaling. This study revealed that circHMGCS1 contributes to NSCLC progression by stabilizing oncogenic HuR and promoting post-transcriptional upregulation of SFPQ, highlighting its potential as a diagnostic and prognostic biomarker for NSCLC.

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来源期刊
The FASEB Journal
The FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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