Transcription factor Dp-1 knockdown downregulates thymidine kinase 1 expression to protect against proliferation and epithelial-mesenchymal transition in cervical cancer

IF 3.9 4区生物学 Q1 GENETICS & HEREDITY

Functional & Integrative Genomics Pub Date : 2023-09-16 DOI:10.1007/s10142-023-01218-6

Mei Wu, Mingji Ye

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Abstract

Thymidine kinase 1 (TK1) level is an independent survival prognostic factor for both premalignant and malignant cervical pathologies. Herein, this study sought to probe the impacts of TK1 on cervical cancer (CC) progression and its underlying mechanism. Transcription factor Dp-1 (TFDP1) and TK1 expression was assessed using qRT-PCR in CC cell lines. After ectopic expression and knockdown experiments, cell counting kit-8 and colony formation assays were adopted to measure cell proliferation, western blot to examine the expression of epithelial-mesenchymal transition (EMT)-related proteins, and Transwell assays to assess cell invasion and migration. The binding of TFDP1 to TK1 was predicted by bioinformatic sites and verified by chromatin immunoprecipitation and dual-luciferase reporter assays. Tumor xenograft experiments in nude mice were performed to validate the influence of TFDP1/TK1 on CC progression in vivo. CC cells had high TK1 and TFDP1 expression. TFDP1 or TK1 knockdown restrained CC cell EMT, invasion, migration, and proliferation. TFDP1 facilitated TK1 expression in CC via transcription. Overexpression of TK1 counteracted the suppressive impacts of TFDP1 knockdown on CC cell malignant behaviors. Moreover, TFDP1 knockdown depressed CC growth in vivo by downregulating TK1. TFDP1 knockdown restricted proliferation and EMT in CC by downregulating TK1 expression.

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转录因子Dp-1敲低可下调胸苷激酶1的表达以防止宫颈癌的增殖和上皮间质转化

胸苷激酶1 (TK1)水平是宫颈癌前病变和恶性病变的独立生存预后因素。本研究旨在探讨TK1对宫颈癌(CC)进展的影响及其潜在机制。采用qRT-PCR技术检测CC细胞株中转录因子Dp-1 (TFDP1)和TK1的表达。异位表达和敲低实验后，采用细胞计数试剂盒-8和集落形成法检测细胞增殖，western blot检测上皮-间质转化(epithelial-mesenchymal transition, EMT)相关蛋白的表达，Transwell检测细胞的侵袭和迁移。生物信息学位点预测了TFDP1与TK1的结合，并通过染色质免疫沉淀和双荧光素酶报告基因检测进行了验证。通过裸鼠肿瘤异种移植实验验证TFDP1/TK1对CC体内进展的影响。CC细胞TK1和TFDP1的表达较高。TFDP1或TK1敲低抑制CC细胞的EMT、侵袭、迁移和增殖。TFDP1通过转录促进TK1在CC中的表达。TK1的过表达抵消了TFDP1敲低对CC细胞恶性行为的抑制作用。此外，TFDP1敲低通过下调TK1抑制CC在体内的生长。TFDP1敲低通过下调TK1表达抑制CC细胞的增殖和EMT。

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来源期刊

Functional & Integrative Genomics 生物-遗传学

CiteScore

3.50

自引率

3.40%

发文量

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?