Cargando…

LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4

Malignant tumors are a grave threat to human health. Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor. China has a high incidence of ESCC, and its morbidity and mortality are higher than the global average. Increasingly, studies have shown that long noncoding RN...

Descripción completa

Detalles Bibliográficos
Autores principales: Niu, Yunfeng, Wang, Gaoyan, Li, Yan, Guo, Wei, Guo, Yanli, Dong, Zhiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712759/
https://www.ncbi.nlm.nih.gov/pubmed/34970490
http://dx.doi.org/10.3389/fonc.2021.773864
_version_ 1784623625284878336
author Niu, Yunfeng
Wang, Gaoyan
Li, Yan
Guo, Wei
Guo, Yanli
Dong, Zhiming
author_facet Niu, Yunfeng
Wang, Gaoyan
Li, Yan
Guo, Wei
Guo, Yanli
Dong, Zhiming
author_sort Niu, Yunfeng
collection PubMed
description Malignant tumors are a grave threat to human health. Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor. China has a high incidence of ESCC, and its morbidity and mortality are higher than the global average. Increasingly, studies have shown that long noncoding RNAs (lncRNAs) play a vital function in the occurrence and development of tumors. Although the biological function of FOXP4-AS1 has been demonstrated in various tumors, the potential molecular mechanism of FOXP4-AS1 in ESCC is still poorly understood. The expression of FOXP4 and FOXP4-AS1 was detected in ESCC by quantitative real-time PCR (qRT–PCR) or SP immunohistochemistry (IHC). shRNA was used to silence gene expression. Apoptosis, cell cycle, MTS, colony formation, invasion and migration assays were employed to explore the biological functions of FOXP4 and FOXP4-AS1. The potential molecular mechanism of FOXP4-AS1 in ESCC was determined by dual-luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP). Here, we demonstrated that FOXP4-AS1 was significantly increased in ESCC tissues and cell lines, associated with lymph node metastasis and TNM staging. Cell function experiments showed that FOXP4-AS1 promoted the proliferation, invasion and migration ability of ESCC cells. The expression of FOXP4-AS1 and FOXP4 in ESCC tissues was positively correlated. Further research found that FOXP4-AS1, upregulated in ESCC, promotes FOXP4 expression by enriching MLL2 and H3K4me3 in the FOXP4 promoter through a “molecular scaffold”. Moreover, FOXP4, a transcription factor of β-catenin, promotes the transcription of β-catenin and ultimately leads to the malignant progression of ESCC. Finally, FOXP4-AS1 may be a new therapeutic target for ESCC.
format Online
Article
Text
id pubmed-8712759
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87127592021-12-29 LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4 Niu, Yunfeng Wang, Gaoyan Li, Yan Guo, Wei Guo, Yanli Dong, Zhiming Front Oncol Oncology Malignant tumors are a grave threat to human health. Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor. China has a high incidence of ESCC, and its morbidity and mortality are higher than the global average. Increasingly, studies have shown that long noncoding RNAs (lncRNAs) play a vital function in the occurrence and development of tumors. Although the biological function of FOXP4-AS1 has been demonstrated in various tumors, the potential molecular mechanism of FOXP4-AS1 in ESCC is still poorly understood. The expression of FOXP4 and FOXP4-AS1 was detected in ESCC by quantitative real-time PCR (qRT–PCR) or SP immunohistochemistry (IHC). shRNA was used to silence gene expression. Apoptosis, cell cycle, MTS, colony formation, invasion and migration assays were employed to explore the biological functions of FOXP4 and FOXP4-AS1. The potential molecular mechanism of FOXP4-AS1 in ESCC was determined by dual-luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP). Here, we demonstrated that FOXP4-AS1 was significantly increased in ESCC tissues and cell lines, associated with lymph node metastasis and TNM staging. Cell function experiments showed that FOXP4-AS1 promoted the proliferation, invasion and migration ability of ESCC cells. The expression of FOXP4-AS1 and FOXP4 in ESCC tissues was positively correlated. Further research found that FOXP4-AS1, upregulated in ESCC, promotes FOXP4 expression by enriching MLL2 and H3K4me3 in the FOXP4 promoter through a “molecular scaffold”. Moreover, FOXP4, a transcription factor of β-catenin, promotes the transcription of β-catenin and ultimately leads to the malignant progression of ESCC. Finally, FOXP4-AS1 may be a new therapeutic target for ESCC. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8712759/ /pubmed/34970490 http://dx.doi.org/10.3389/fonc.2021.773864 Text en Copyright © 2021 Niu, Wang, Li, Guo, Guo and Dong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Niu, Yunfeng
Wang, Gaoyan
Li, Yan
Guo, Wei
Guo, Yanli
Dong, Zhiming
LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4
title LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4
title_full LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4
title_fullStr LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4
title_full_unstemmed LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4
title_short LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4
title_sort lncrna foxp4-as1 promotes the progression of esophageal squamous cell carcinoma by interacting with mll2/h3k4me3 to upregulate foxp4
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712759/
https://www.ncbi.nlm.nih.gov/pubmed/34970490
http://dx.doi.org/10.3389/fonc.2021.773864
work_keys_str_mv AT niuyunfeng lncrnafoxp4as1promotestheprogressionofesophagealsquamouscellcarcinomabyinteractingwithmll2h3k4me3toupregulatefoxp4
AT wanggaoyan lncrnafoxp4as1promotestheprogressionofesophagealsquamouscellcarcinomabyinteractingwithmll2h3k4me3toupregulatefoxp4
AT liyan lncrnafoxp4as1promotestheprogressionofesophagealsquamouscellcarcinomabyinteractingwithmll2h3k4me3toupregulatefoxp4
AT guowei lncrnafoxp4as1promotestheprogressionofesophagealsquamouscellcarcinomabyinteractingwithmll2h3k4me3toupregulatefoxp4
AT guoyanli lncrnafoxp4as1promotestheprogressionofesophagealsquamouscellcarcinomabyinteractingwithmll2h3k4me3toupregulatefoxp4
AT dongzhiming lncrnafoxp4as1promotestheprogressionofesophagealsquamouscellcarcinomabyinteractingwithmll2h3k4me3toupregulatefoxp4