Visinin-like 1, a novel target gene of the Wnt/β-catenin signaling pathway, is involved in apoptosis resistance in colorectal cancer.
Visinin-like 1 (VSNL1)
Wnt/β-catenin signaling
apoptosis
colorectal cancer
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
14
03
2023
received:
10
11
2022
accepted:
07
04
2023
medline:
4
7
2023
pubmed:
25
4
2023
entrez:
25
04
2023
Statut:
ppublish
Résumé
Abnormal activation of Wnt/β-catenin signaling is associated with various aspects of cancer development. This study explored the roles of novel target genes of the Wnt/β-catenin signaling pathway in cancer cells. Using the haploid chronic myelogenous leukemia cell line HAP1, RNA sequencing (RNA-seq) was performed to identify genes whose expression was increased by APC disruption and reversed by β-catenin knockdown (KD). The regulatory mechanism and function of one of the candidate genes was investigated in colorectal cancer (CRC) cells. In total, 64 candidate genes whose expression was regulated by Wnt/β-catenin signaling were identified. Of these candidate genes, the expression levels of six were reduced by β-catenin KD in HCT116 CRC cells in our previous microarray. One of these genes was Visinin-like 1 (VSNL1), which belongs to the neuronal calcium-sensor gene family. The expression of VSNL1 was regulated by the β-catenin/TCF7L2 complex via two TCF7L2-binding elements in intron 1. VSNL1 KD-induced apoptosis in VSNL1-positive CRC cells. Additionally, forced expression of wild-type VSNL1, but not a myristoylation, Ca Our findings suggest that VSNL1, a novel target gene of the Wnt/β-catenin signaling pathway, is associated with apoptosis resistance in CRC cells.
Sections du résumé
BACKGROUND
Abnormal activation of Wnt/β-catenin signaling is associated with various aspects of cancer development. This study explored the roles of novel target genes of the Wnt/β-catenin signaling pathway in cancer cells.
METHODS
Using the haploid chronic myelogenous leukemia cell line HAP1, RNA sequencing (RNA-seq) was performed to identify genes whose expression was increased by APC disruption and reversed by β-catenin knockdown (KD). The regulatory mechanism and function of one of the candidate genes was investigated in colorectal cancer (CRC) cells.
RESULTS
In total, 64 candidate genes whose expression was regulated by Wnt/β-catenin signaling were identified. Of these candidate genes, the expression levels of six were reduced by β-catenin KD in HCT116 CRC cells in our previous microarray. One of these genes was Visinin-like 1 (VSNL1), which belongs to the neuronal calcium-sensor gene family. The expression of VSNL1 was regulated by the β-catenin/TCF7L2 complex via two TCF7L2-binding elements in intron 1. VSNL1 KD-induced apoptosis in VSNL1-positive CRC cells. Additionally, forced expression of wild-type VSNL1, but not a myristoylation, Ca
CONCLUSION
Our findings suggest that VSNL1, a novel target gene of the Wnt/β-catenin signaling pathway, is associated with apoptosis resistance in CRC cells.
Identifiants
pubmed: 37096864
doi: 10.1002/cam4.5970
pmc: PMC10315817
doi:
Substances chimiques
beta Catenin
0
visinin
0
VSNL1 protein, human
0
Neurocalcin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13426-13437Informations de copyright
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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