KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis

Abstract Altered Krüppel‐like factor 9 (KLF9) expression can regulate the progression of several cancers, including renal cell carcinoma (RCC). This study was conducted to investigate the role of KLF9 in the proliferation, invasion, and migration of RCC cells via regulation of stromal cell‐derived f...

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Main Authors: Peng Yu, Long Cheng, Wei‐Mu Xia, Ding‐Yi Liu, Jia‐Shun Yu, Yan‐Feng Zhou, Yong‐Jun Zheng
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:Kaohsiung Journal of Medical Sciences
Subjects:
Online Access:https://doi.org/10.1002/kjm2.12671
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author Peng Yu
Long Cheng
Wei‐Mu Xia
Ding‐Yi Liu
Jia‐Shun Yu
Yan‐Feng Zhou
Yong‐Jun Zheng
author_facet Peng Yu
Long Cheng
Wei‐Mu Xia
Ding‐Yi Liu
Jia‐Shun Yu
Yan‐Feng Zhou
Yong‐Jun Zheng
author_sort Peng Yu
collection DOAJ
description Abstract Altered Krüppel‐like factor 9 (KLF9) expression can regulate the progression of several cancers, including renal cell carcinoma (RCC). This study was conducted to investigate the role of KLF9 in the proliferation, invasion, and migration of RCC cells via regulation of stromal cell‐derived factor‐1 (SDF‐1)/CXC chemokine receptor 4 (CXCR4). The expression patterns of KLF9, SDF‐1, and CXCR4 in the experimental cell lines were determined by real‐time quantitative polymerase chain reaction and Western blotting. After transfection of the KLF9 siRNA and KLF9 pcDNA, cell proliferation, invasion, and migration were evaluated by experiments including cell counting kit‐8, colony formation, and Transwell assays. The binding of KLF9 to the SDF‐1 promoter was analyzed by chromatin immunoprecipitation and dual‐luciferase assay. The rescue experiment was performed using the recombinant SDF‐1 protein and KLF9 pcDNA. KLF9 was downregulated in the RCC cells. KLF9 knockdown induced the proliferation, invasion, and migration of RCC cells, whereas KLF9 overexpression elicited the opposite roles. Mechanically, KLF9 bound to the SDF‐1 promoter, repressed SDF‐1 transcription, and reduced the SDF‐1/CXCR4 expression levels. Activation of the SDF‐1/CXCR4 axis attenuated the inhibitory role of KLF9 overexpression in RCC cell growth. Ordinarily, KLF9 suppressed the proliferation, invasion, and migration of RCC cells by repressing the SDF‐1/CXCR4 signaling.
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spelling doaj.art-3b8f1a4cfbb142e7b00d7c6a56cec0762023-06-08T13:32:18ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-06-0139658759510.1002/kjm2.12671KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axisPeng Yu0Long Cheng1Wei‐Mu Xia2Ding‐Yi Liu3Jia‐Shun Yu4Yan‐Feng Zhou5Yong‐Jun Zheng6Department of Urology Shanghai Punan Hospital of Pudong New District Shanghai ChinaDepartment of Cardiology Fudan University Jinshan Hospital Shanghai ChinaDepartment of Urology Shanghai Punan Hospital of Pudong New District Shanghai ChinaDepartment of Urology Shanghai Punan Hospital of Pudong New District Shanghai ChinaDepartment of Urology Shanghai Punan Hospital of Pudong New District Shanghai ChinaDepartment of Urology Shanghai Punan Hospital of Pudong New District Shanghai ChinaDepartment of Urology Shanghai Punan Hospital of Pudong New District Shanghai ChinaAbstract Altered Krüppel‐like factor 9 (KLF9) expression can regulate the progression of several cancers, including renal cell carcinoma (RCC). This study was conducted to investigate the role of KLF9 in the proliferation, invasion, and migration of RCC cells via regulation of stromal cell‐derived factor‐1 (SDF‐1)/CXC chemokine receptor 4 (CXCR4). The expression patterns of KLF9, SDF‐1, and CXCR4 in the experimental cell lines were determined by real‐time quantitative polymerase chain reaction and Western blotting. After transfection of the KLF9 siRNA and KLF9 pcDNA, cell proliferation, invasion, and migration were evaluated by experiments including cell counting kit‐8, colony formation, and Transwell assays. The binding of KLF9 to the SDF‐1 promoter was analyzed by chromatin immunoprecipitation and dual‐luciferase assay. The rescue experiment was performed using the recombinant SDF‐1 protein and KLF9 pcDNA. KLF9 was downregulated in the RCC cells. KLF9 knockdown induced the proliferation, invasion, and migration of RCC cells, whereas KLF9 overexpression elicited the opposite roles. Mechanically, KLF9 bound to the SDF‐1 promoter, repressed SDF‐1 transcription, and reduced the SDF‐1/CXCR4 expression levels. Activation of the SDF‐1/CXCR4 axis attenuated the inhibitory role of KLF9 overexpression in RCC cell growth. Ordinarily, KLF9 suppressed the proliferation, invasion, and migration of RCC cells by repressing the SDF‐1/CXCR4 signaling.https://doi.org/10.1002/kjm2.12671invasionKLF9migrationproliferationrenal cell carcinoma
spellingShingle Peng Yu
Long Cheng
Wei‐Mu Xia
Ding‐Yi Liu
Jia‐Shun Yu
Yan‐Feng Zhou
Yong‐Jun Zheng
KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis
Kaohsiung Journal of Medical Sciences
invasion
KLF9
migration
proliferation
renal cell carcinoma
title KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis
title_full KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis
title_fullStr KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis
title_full_unstemmed KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis
title_short KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF‐1/CXCR4 axis
title_sort klf9 inhibits the proliferation invasion and migration of renal cell carcinoma through the sdf 1 cxcr4 axis
topic invasion
KLF9
migration
proliferation
renal cell carcinoma
url https://doi.org/10.1002/kjm2.12671
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