KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation

Gastric cancer is the third leading cause of cancer death worldwide. In this study, we tried to clarify the function of <i>KLF5</i> in gastric cancer. Copy number variation (CNV) and the expression of <i>KLF5</i> were interrogated in public datasets. The clinical significance...

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Main Authors: Wei Chen, Jian Zhang, Huafeng Fu, Xun Hou, Qiao Su, Yulong He, Dongjie Yang
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/5/1002
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author Wei Chen
Jian Zhang
Huafeng Fu
Xun Hou
Qiao Su
Yulong He
Dongjie Yang
author_facet Wei Chen
Jian Zhang
Huafeng Fu
Xun Hou
Qiao Su
Yulong He
Dongjie Yang
author_sort Wei Chen
collection DOAJ
description Gastric cancer is the third leading cause of cancer death worldwide. In this study, we tried to clarify the function of <i>KLF5</i> in gastric cancer. Copy number variation (CNV) and the expression of <i>KLF5</i> were interrogated in public datasets. The clinical significance of <i>KLF5</i> amplification and gene expression in gastric cancer were evaluated. The function of <i>KLF5</i> in cell proliferation was studied in gastric cancer cell lines and organoids. We found that <i>KLF5</i> amplification mainly occurred in the chromosome instable tumors (CIN) and was significantly associated with <i>TP53</i> mutation. In addition, higher <i>KLF5</i> expression correlated with more locally invasive gastric cancer and higher T stage. Next, a <i>KLF5</i> gene expression signature was curated. The genes in the signature were involved in cell development, cell cycle regulation, cell death, suggesting potential roles played by <i>KLF5</i>. Functional studies using siRNAs revealed that <i>KLF5</i> was essential for the proliferation of gastric cancer cells. Finally, using gastric organoid models, we revealed that the proliferation of organoids was significantly inhibited after the down regulation of <i>KLF5</i>. Our study revealed that <i>KLF5</i> was amplified and over-expressed in gastric cancer, and it may play an oncogene-like role in gastric cancer by supporting cell proliferation.
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spelling doaj.art-0418cde4b84144599293187e32f62bf82023-11-21T16:57:37ZengMDPI AGCells2073-44092021-04-01105100210.3390/cells10051002KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell ProliferationWei Chen0Jian Zhang1Huafeng Fu2Xun Hou3Qiao Su4Yulong He5Dongjie Yang6Center for Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCenter for Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCenter for Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCenter for Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaAnimal Experiment Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCenter for Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCenter for Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaGastric cancer is the third leading cause of cancer death worldwide. In this study, we tried to clarify the function of <i>KLF5</i> in gastric cancer. Copy number variation (CNV) and the expression of <i>KLF5</i> were interrogated in public datasets. The clinical significance of <i>KLF5</i> amplification and gene expression in gastric cancer were evaluated. The function of <i>KLF5</i> in cell proliferation was studied in gastric cancer cell lines and organoids. We found that <i>KLF5</i> amplification mainly occurred in the chromosome instable tumors (CIN) and was significantly associated with <i>TP53</i> mutation. In addition, higher <i>KLF5</i> expression correlated with more locally invasive gastric cancer and higher T stage. Next, a <i>KLF5</i> gene expression signature was curated. The genes in the signature were involved in cell development, cell cycle regulation, cell death, suggesting potential roles played by <i>KLF5</i>. Functional studies using siRNAs revealed that <i>KLF5</i> was essential for the proliferation of gastric cancer cells. Finally, using gastric organoid models, we revealed that the proliferation of organoids was significantly inhibited after the down regulation of <i>KLF5</i>. Our study revealed that <i>KLF5</i> was amplified and over-expressed in gastric cancer, and it may play an oncogene-like role in gastric cancer by supporting cell proliferation.https://www.mdpi.com/2073-4409/10/5/1002KLF5gastric cancercopy number variationTCGA
spellingShingle Wei Chen
Jian Zhang
Huafeng Fu
Xun Hou
Qiao Su
Yulong He
Dongjie Yang
KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation
Cells
KLF5
gastric cancer
copy number variation
TCGA
title KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation
title_full KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation
title_fullStr KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation
title_full_unstemmed KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation
title_short KLF5 Is Activated by Gene Amplification in Gastric Cancer and Is Essential for Gastric Cell Proliferation
title_sort klf5 is activated by gene amplification in gastric cancer and is essential for gastric cell proliferation
topic KLF5
gastric cancer
copy number variation
TCGA
url https://www.mdpi.com/2073-4409/10/5/1002
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