TBP 激活 DCBLD1 转录,促进宫颈癌细胞周期进展

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY
Zhigang Shen, Mei Li, He Zhu, Tao Song
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引用次数: 0

摘要

含类盘蛋白、CUB和LCCL结构域(DCBLD)的蛋白与人类癌症的不良预后有关。本研究探讨了DCBLD1在宫颈癌(CC)发病过程中的功能及其相关机制。通过生物信息学分析发现,DCBLD1是宫颈癌中调控异常的基因。免疫组化和 RT-qPCR 检测显示 DCBLD1 在 CC 标本和细胞中表达增加。人工敲除 DCBLD1 可阻止细胞的增殖、侵袭和迁移,同时促进细胞凋亡并诱导细胞周期停滞在 G1 期。经过生物信息学预测以及随后的染色质免疫沉淀和荧光素酶报告实验,发现TATA-box结合蛋白(TBP)是一种转录因子,能与DCBLD1启动子区域结合以激活转录。TBP的敲除同样阻断了CC细胞的恶性特性并诱导细胞周期停滞,但这些变化在进一步过表达DCBLD1后被逆转。为进行体内验证,还生成了异种移植小鼠肿瘤。一致的是,TBP 敲除抑制了裸鼠 CC 细胞的致瘤活性,但 DCBLD1 的过表达恢复了其致瘤活性。总之,这项研究提供了新的证据,证明 TBP 介导的 DCBLD1 激活与细胞周期和 CC 进展相关。TBP和DCBLD1可作为治疗CC的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TBP activates DCBLD1 transcription to promote cell cycle progression in cervical cancer

Discoidin, CUB, and LCCL domain-containing (DCBLD) proteins have been associated with poor prognosis of human cancers. This study investigated the function of DCBLD1 in the development of cervical cancer (CC) and explored its associated mechanism. DCBLD1 was identified as a dysregulated gene in CC via bioinformatics analysis. Immunohistochemistry and RT-qPCR assays revealed increased DCBLD1 expression in CC specimens and cells. Artificial DCBLD1 knockdown blocked the proliferation, invasion, and migration of cells, while promoting cell apoptosis and inducing cell cycle arrest in the G1 phase. Following bioinformatic predictions and subsequent chromatin-immunoprecipitation and luciferase reporter assays, TATA-box binding protein (TBP) was found to be a transcription factor that binds to the DCBLD1 promoter region for transcriptional activation. Knockdown of TBP similarly blocked the malignant properties of CC cells and induced cell cycle arrest, but these changes were reversed by further DCBLD1 overexpression. Xenograft mouse tumors were generated for in vivo validation. Consistently, the tumorigenic activity of CC cells in nude mice was suppressed by TBP knockdown, but restored by DCBLD1 overexpression. In conclusion, this study provides novel evidence that TBP-mediated DCBLD1 activation is correlated with cell cycle and CC progression. TBP and DCBLD1 may serve as potential therapeutic targets for CC management.

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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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