KLF5 silencing restrains proliferation, invasion, migration and angiogenesis of gallbladder carcinoma cells by transcriptional regulation of PDGFA.

IF 2.7 3区 医学 Q3 ONCOLOGY
Xiaowei Lu, Kui Hu, Dandan Zhang, Xuefeng Yin, Jifeng Nie, Kai Zhao
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引用次数: 0

Abstract

Background: Krüppel-like factor 5 (KLF5) is recognized as a tumor mediator in multiple types of tumors. Nevertheless, whether KLF5 plays a role in gallbladder cancer (GBC) remains to be elucidated. This study aims to clarify the role of KLF5 in the proliferation, migration and angiogenesis in GBC cells.

Methods: The expressions of KLF5 and platelet-derived growth factor subunit A (PDGFA) in GBC cell lines were analyzed by qRT-PCR and western blot assay. Cell proliferation was assessed utilizing the Cell Counting Kit-8 assay and EDU staining. Cell apoptosis was evaluated using flow cytometry, and apoptosis-related proteins was examined by western blotting. The migratory and invasive capabilities were evaluated utilizing wound healing and Transwell. Angiogenesis was assessed by ELISA, tube formation assay and western blot. The interaction between KLF5 and PDGFA was confirmed by ChIP assay, as well as luciferase reporter assay.

Results: In this study, we discovered that the levels of KLF5 and PDGFA were upregulated in GBC cells. Silencing of KLF5 reduced the viability and suppressed the proliferation of GBC cells, as well as promoting the apoptosis. In addition, KLF5 silencing restrained the invasion and migration and angiogenesis in NOZ and GBC-SD cells. KLF5 transcription activated PDGFA expression and KLF5 was proved to bind to PDGFA promoter in NOZ cells. Following the silencing of PDGFA, the proliferation, invasion, migration, angiogenesis and apoptosis exhibited similar changes to KLF5 silencing. Additionally, PDGFA overexpression reversed the effects of KLF5 silencing on NOZ cells.

Conclusion: Collectively, our results suggest that KLF5 regulates GBC cell proliferation, invasion, migration, angiogenesis, as well as apoptosis, via mediating PDGFA transcriptionally, which might provide a novel therapeutic strategy for treatment of human GBC.

KLF5沉默通过转录调控PDGFA抑制胆囊癌细胞的增殖、侵袭、迁移和血管生成。
背景:kr ppel样因子5 (KLF5)被认为是多种类型肿瘤的肿瘤介质。然而,KLF5是否在胆囊癌(GBC)中发挥作用仍有待阐明。本研究旨在阐明KLF5在GBC细胞增殖、迁移和血管生成中的作用。方法:采用qRT-PCR和western blot方法检测GBC细胞株中KLF5和血小板源性生长因子亚单位A (PDGFA)的表达。利用细胞计数试剂盒-8法和EDU染色评估细胞增殖。流式细胞术检测细胞凋亡,western blotting检测细胞凋亡相关蛋白。利用伤口愈合和Transwell评估迁移和侵袭能力。采用酶联免疫吸附法(ELISA)、成管试验和western blot检测血管新生情况。通过ChIP实验和荧光素酶报告基因实验证实了KLF5与PDGFA的相互作用。结果:在本研究中,我们发现GBC细胞中KLF5和PDGFA水平上调。KLF5的沉默降低了GBC细胞的活力,抑制了GBC细胞的增殖,促进了GBC细胞的凋亡。此外,KLF5沉默抑制了NOZ和GBC-SD细胞的侵袭迁移和血管生成。KLF5转录激活PDGFA的表达,KLF5在NOZ细胞中被证实与PDGFA启动子结合。PDGFA沉默后,细胞的增殖、侵袭、迁移、血管生成和凋亡的变化与KLF5沉默后相似。此外,PDGFA过表达逆转了KLF5沉默对NOZ细胞的影响。结论:综上所述,我们的研究结果表明,KLF5通过介导PDGFA转录调控GBC细胞的增殖、侵袭、迁移、血管生成和凋亡,可能为治疗人GBC提供一种新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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