Functional Analysis and Clinical Significance of Chloride Channel 2 Expression in Esophageal Squamous Cell Carcinoma.
Apoptosis
Biomarkers, Tumor
/ genetics
CLC-2 Chloride Channels
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Chloride Channels
/ genetics
Esophageal Neoplasms
/ genetics
Esophageal Squamous Cell Carcinoma
/ genetics
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
Humans
Prognosis
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
13
07
2020
accepted:
13
01
2021
pubmed:
11
2
2021
medline:
12
8
2021
entrez:
10
2
2021
Statut:
ppublish
Résumé
Chloride channel 2 (CLCN2) was recently shown to affect tumor behavior. The present study examined the functions of CLCN2 in the regulation of genes that play a role in tumor progression, as well as its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). Knockdown experiments were conducted using CLCN2-small-interfering RNA, and changes in proliferation, survival, and cellular movement in human ESCC cell lines were investigated. A microarray analysis of gene expression profiles in CLCN2-depleted ESCC cells was conducted. Fifty-four primary ESCC samples were examined by immunohistochemistry (IHC). The strong expression of CLCN2 was detected in TE5 and KYSE70 cells. Downregulated expression of CLCN2 enhanced proliferation and decreased apoptosis, whereas its upregulation inhibited proliferation and increased apoptosis. The effects of lubiprostone, a CLCN2 activator, were also investigated. In lubiprostone-treated cells, proliferation was inhibited and apoptosis was increased. The microarray analysis demonstrated that interferon (IFN) signaling-related genes were downregulated in CLCN2-depleted cells. IHC showed the presence of CLCN2 in the cytoplasm and cell membranes of ESCC cells. The prognostic analysis revealed a relationship between weak CLCN2 expression and shorter overall survival. The present results indicate that tumor progression is regulated by CLCN2 through its effects on IFN signaling. Furthermore, weak CLCN2 expression was associated with poorer outcomes in ESCC patients. The present study will contribute to a clearer understanding of the role of CLCN2 as a mediator of ESCC, as well as its use as a biomarker for this cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Chloride channel 2 (CLCN2) was recently shown to affect tumor behavior. The present study examined the functions of CLCN2 in the regulation of genes that play a role in tumor progression, as well as its clinicopathological significance in esophageal squamous cell carcinoma (ESCC).
METHODS
METHODS
Knockdown experiments were conducted using CLCN2-small-interfering RNA, and changes in proliferation, survival, and cellular movement in human ESCC cell lines were investigated. A microarray analysis of gene expression profiles in CLCN2-depleted ESCC cells was conducted. Fifty-four primary ESCC samples were examined by immunohistochemistry (IHC).
RESULTS
RESULTS
The strong expression of CLCN2 was detected in TE5 and KYSE70 cells. Downregulated expression of CLCN2 enhanced proliferation and decreased apoptosis, whereas its upregulation inhibited proliferation and increased apoptosis. The effects of lubiprostone, a CLCN2 activator, were also investigated. In lubiprostone-treated cells, proliferation was inhibited and apoptosis was increased. The microarray analysis demonstrated that interferon (IFN) signaling-related genes were downregulated in CLCN2-depleted cells. IHC showed the presence of CLCN2 in the cytoplasm and cell membranes of ESCC cells. The prognostic analysis revealed a relationship between weak CLCN2 expression and shorter overall survival.
CONCLUSIONS
CONCLUSIONS
The present results indicate that tumor progression is regulated by CLCN2 through its effects on IFN signaling. Furthermore, weak CLCN2 expression was associated with poorer outcomes in ESCC patients. The present study will contribute to a clearer understanding of the role of CLCN2 as a mediator of ESCC, as well as its use as a biomarker for this cancer.
Identifiants
pubmed: 33565032
doi: 10.1245/s10434-021-09659-8
pii: 10.1245/s10434-021-09659-8
doi:
Substances chimiques
Biomarkers, Tumor
0
CLC-2 Chloride Channels
0
Chloride Channels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5384-5397Subventions
Organisme : Japan Society for the Promotion of Science
ID : Grant-in-Aid for Young Scientists/ 19K18160
Organisme : Japan Society for the Promotion of Science
ID : Grants-in-Aid for Scientific Research/ 17K10602
Organisme : Japan Society for the Promotion of Science
ID : 17K10710
Organisme : Japan Society for the Promotion of Science
ID : 18K08628
Organisme : Japan Society for the Promotion of Science
ID : 18K08689
Organisme : Japan Society for the Promotion of Science
ID : 19K09182
Organisme : Japan Society for the Promotion of Science
ID : 19K09202
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. Society of Surgical Oncology.
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