H3K27me3 Inactivates SFRP1 to Promote Cell Proliferation via Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma.
Humans
Esophageal Squamous Cell Carcinoma
/ pathology
Histones
/ metabolism
Wnt Signaling Pathway
/ genetics
Esophageal Neoplasms
/ pathology
Cell Line, Tumor
Cell Proliferation
/ genetics
Cell Movement
/ genetics
Gene Expression Regulation, Neoplastic
Membrane Proteins
/ genetics
Intercellular Signaling Peptides and Proteins
/ genetics
Cell proliferation
Esophageal squamous cell carcinoma
H3K27me3
SFRP1
Wnt/β-catenin signaling pathway
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
31
07
2022
accepted:
21
02
2023
medline:
18
5
2023
pubmed:
19
3
2023
entrez:
18
3
2023
Statut:
ppublish
Résumé
Histone methylations are generally considered to play an important role in multiple cancers by regulating cancer-related genes. This study aims to investigate the effects of H3K27me3-mediated inactivation of tumor suppressor gene SFRP1 and its function in esophageal squamous cell carcinoma (ESCC). We performed ChIP-seq on H3K27me3-enriched genomic DNA fragments in ESCC cells to screen out tumor suppressor genes that may be regulated by H3K27me3. ChIP-qPCR and Western blot were employed to explore the regulating mechanisms between H3K27me3 and SFRP1. Expression level of SFRP1 was assessed by quantitative real-time polymerase chain reaction (q-PCR) in 29 pairs of ESCC surgical samples. SFRP1 function in ESCC cells were detected by cell proliferation assay, colony formation assay and wound-healing assay. Our results indicated that H3K27me3 was widely distributed in the genome of ESCC cells. Specifically, we found that H3K27me3 deposited on the upstream region of SFRP1 promoter and inactivated SFRP1 expression. Furthermore, we found SFRP1 was significantly down-regulated in ESCC tissues compared with the adjacent non-tumor tissues, and SFRP1 expression was significantly associated with TNM stage and lymph node metastasis. In vitro cell-based assay indicated that over-expression of SFRP1 significantly suppressed cell proliferation and negatively correlated with the expression of β-catenin in the nucleus. Our study revealed a previously unrecognized finding that H3K27me3-mediated SFRP1 inhibit the cell proliferation of ESCC through inactivation of Wnt/β-catenin signaling pathway.
Sections du résumé
BACKGROUND
Histone methylations are generally considered to play an important role in multiple cancers by regulating cancer-related genes.
AIMS
This study aims to investigate the effects of H3K27me3-mediated inactivation of tumor suppressor gene SFRP1 and its function in esophageal squamous cell carcinoma (ESCC).
METHODS
We performed ChIP-seq on H3K27me3-enriched genomic DNA fragments in ESCC cells to screen out tumor suppressor genes that may be regulated by H3K27me3. ChIP-qPCR and Western blot were employed to explore the regulating mechanisms between H3K27me3 and SFRP1. Expression level of SFRP1 was assessed by quantitative real-time polymerase chain reaction (q-PCR) in 29 pairs of ESCC surgical samples. SFRP1 function in ESCC cells were detected by cell proliferation assay, colony formation assay and wound-healing assay.
RESULTS
Our results indicated that H3K27me3 was widely distributed in the genome of ESCC cells. Specifically, we found that H3K27me3 deposited on the upstream region of SFRP1 promoter and inactivated SFRP1 expression. Furthermore, we found SFRP1 was significantly down-regulated in ESCC tissues compared with the adjacent non-tumor tissues, and SFRP1 expression was significantly associated with TNM stage and lymph node metastasis. In vitro cell-based assay indicated that over-expression of SFRP1 significantly suppressed cell proliferation and negatively correlated with the expression of β-catenin in the nucleus.
CONCLUSIONS
Our study revealed a previously unrecognized finding that H3K27me3-mediated SFRP1 inhibit the cell proliferation of ESCC through inactivation of Wnt/β-catenin signaling pathway.
Identifiants
pubmed: 36933113
doi: 10.1007/s10620-023-07892-7
pii: 10.1007/s10620-023-07892-7
doi:
Substances chimiques
Histones
0
SFRP1 protein, human
0
Membrane Proteins
0
Intercellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2463-2473Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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