Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration

Jiafa Wu,1 Dongping Luo,2 Shengnan Li3 1School of Food and Bioengineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3School of Medicine, Henan Poly...

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Main Authors: Wu J, Luo D, Li S
Format: Article
Language:English
Published: Dove Medical Press 2022-08-01
Series:Breast Cancer: Targets and Therapy
Subjects:
Online Access:https://www.dovepress.com/ovo-like-zinc-finger-2-ovol2-suppresses-breast-cancer-stem-cell-traits-peer-reviewed-fulltext-article-BCTT
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author Wu J
Luo D
Li S
author_facet Wu J
Luo D
Li S
author_sort Wu J
collection DOAJ
description Jiafa Wu,1 Dongping Luo,2 Shengnan Li3 1School of Food and Bioengineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3School of Medicine, Henan Polytechnic University, Jiaozuo, People’s Republic of ChinaCorrespondence: Jiafa Wu, School of Food and Bioengineering, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, People’s Republic of China, Email wujiafa@haust.edu.cnBackground: Breast cancer stem cells (BCSCs) are associated with tumor initiation, invasion, metastasis and drug resistance. It is known that many proteins and signaling pathways are involved in the regulation of BCSCs, however, much more efforts are needed to understand BCSCs comprehensively. Tumor-infiltrating immune cells are important in cancer treatment efficacy and patient prognosis. We tried to identify potential suppressor of BCSCs and analyze its correlation with various immune cells infiltration by bioinformatic and experimental methods.Methods: Expression level and methylation state of OVOL2 were analyzed by tools from bc-GenExMiner v4.8 and UALCAN databases. The Kaplan–Meier plotter was applied to evaluate the prognostic values of OVOL2. Gene expression datasets (GSE7515, GSE15192) were selected to analyze differentially expressed genes (DEGs) related to BCSCs. GO and KEGG pathway analyses of DEGs were conducted. MCODE app plugin of Cytoscape was used to screen modules in PPI network of downregulated DEGs. Correlation of OVOL2 expression with infiltrating immune cells was evaluated by TIMER 2.0. Experiments were conducted to verify whether OVOL2 could inhibit stemness traits of breast cancer cell MDA-MB-231.Results: The expression level of OVOL2 in basal/TNBC was significantly lower than that of other subtypes. Survival analyses indicated that high expression of OVOL2 was associated with favorable prognosis. GO and KEGG pathway analyses for upregulated and downregulated DEGs were conducted. The top three clusters of downregulated DEGs showed that tight junction and chemokines may play important roles in BCSCs. OVOL2 is one module of clusters. OVOL2 expression is correlated with various immune cells infiltration. Experiments showed that OVOL2 suppresses CD44+/CD24− ratio and mammospheres formation of MDA-MB-231.Conclusion: OVOL2 may play an important role in the regulation of breast cancer stemness and immune cell infiltration, and is likely to be a target for the treatment of breast cancer.Keywords: OVOL2, gene ontology, KEGG pathway, BCSCs, immune cell infiltration
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spelling doaj.art-1fe03520042a468b962a1f0506efa5292022-12-22T03:07:06ZengDove Medical PressBreast Cancer: Targets and Therapy1179-13142022-08-01Volume 1421122777387Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells InfiltrationWu JLuo DLi SJiafa Wu,1 Dongping Luo,2 Shengnan Li3 1School of Food and Bioengineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3School of Medicine, Henan Polytechnic University, Jiaozuo, People’s Republic of ChinaCorrespondence: Jiafa Wu, School of Food and Bioengineering, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, People’s Republic of China, Email wujiafa@haust.edu.cnBackground: Breast cancer stem cells (BCSCs) are associated with tumor initiation, invasion, metastasis and drug resistance. It is known that many proteins and signaling pathways are involved in the regulation of BCSCs, however, much more efforts are needed to understand BCSCs comprehensively. Tumor-infiltrating immune cells are important in cancer treatment efficacy and patient prognosis. We tried to identify potential suppressor of BCSCs and analyze its correlation with various immune cells infiltration by bioinformatic and experimental methods.Methods: Expression level and methylation state of OVOL2 were analyzed by tools from bc-GenExMiner v4.8 and UALCAN databases. The Kaplan–Meier plotter was applied to evaluate the prognostic values of OVOL2. Gene expression datasets (GSE7515, GSE15192) were selected to analyze differentially expressed genes (DEGs) related to BCSCs. GO and KEGG pathway analyses of DEGs were conducted. MCODE app plugin of Cytoscape was used to screen modules in PPI network of downregulated DEGs. Correlation of OVOL2 expression with infiltrating immune cells was evaluated by TIMER 2.0. Experiments were conducted to verify whether OVOL2 could inhibit stemness traits of breast cancer cell MDA-MB-231.Results: The expression level of OVOL2 in basal/TNBC was significantly lower than that of other subtypes. Survival analyses indicated that high expression of OVOL2 was associated with favorable prognosis. GO and KEGG pathway analyses for upregulated and downregulated DEGs were conducted. The top three clusters of downregulated DEGs showed that tight junction and chemokines may play important roles in BCSCs. OVOL2 is one module of clusters. OVOL2 expression is correlated with various immune cells infiltration. Experiments showed that OVOL2 suppresses CD44+/CD24− ratio and mammospheres formation of MDA-MB-231.Conclusion: OVOL2 may play an important role in the regulation of breast cancer stemness and immune cell infiltration, and is likely to be a target for the treatment of breast cancer.Keywords: OVOL2, gene ontology, KEGG pathway, BCSCs, immune cell infiltrationhttps://www.dovepress.com/ovo-like-zinc-finger-2-ovol2-suppresses-breast-cancer-stem-cell-traits-peer-reviewed-fulltext-article-BCTTovol2gene ontologykegg pathwaybcscsimmune cell infiltration
spellingShingle Wu J
Luo D
Li S
Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration
Breast Cancer: Targets and Therapy
ovol2
gene ontology
kegg pathway
bcscs
immune cell infiltration
title Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration
title_full Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration
title_fullStr Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration
title_full_unstemmed Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration
title_short Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration
title_sort ovo like zinc finger 2 ovol2 suppresses breast cancer stem cell traits and correlates with immune cells infiltration
topic ovol2
gene ontology
kegg pathway
bcscs
immune cell infiltration
url https://www.dovepress.com/ovo-like-zinc-finger-2-ovol2-suppresses-breast-cancer-stem-cell-traits-peer-reviewed-fulltext-article-BCTT
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