CLASRP oncogene as a novel target for colorectal cancer.
Apoptosis
CLASRP
Clk inhibitors
Colorectal cancer
Promotional oncogene
Journal
Functional & integrative genomics
ISSN: 1438-7948
Titre abrégé: Funct Integr Genomics
Pays: Germany
ID NLM: 100939343
Informations de publication
Date de publication:
02 Sep 2023
02 Sep 2023
Historique:
received:
31
05
2023
accepted:
11
08
2023
revised:
04
08
2023
medline:
5
9
2023
pubmed:
4
9
2023
entrez:
2
9
2023
Statut:
epublish
Résumé
Clk4-associated serine/arginine-rich protein (CLASRP), an alternative splicing regulator, may be involved in the development and progression of cancer by regulating the activity of the CDC-like kinase (Clk) family. This study explored the biological function of CLASRP in colorectal cancer (CRC). The expression of CLASRP, which is associated with clinicopathological features, was analysed in CRC tissues and paired noncancer tissues by RT-PCR. The roles of CLASRP were investigated in CRC cells transfected with plasmids or shRNA through proliferation, migration and invasion assays in vitro and a xenograft model in vivo. Apoptosis was analysed using CLASRP-overexpressing CRC cells by western blotting. Clk inhibitors were used to perform functional research on CLASRP in CLASRP-overexpressing CRC cells. CLASRP was significantly upregulated in CRC cell lines, while high CLASRP expression was correlated with metastasis in CRC patients. Functionally, overexpression of CLASRP significantly promoted the proliferation, migration and invasion of CRC cells in vitro and tumour growth in vivo. Mechanistically, the proliferation, migration and invasion of CLASRP-overexpressing CRC cells were inhibited by Clk inhibitors, accompanied by low expression of CLASRP at the gene and protein levels. Clk inhibitors induced apoptosis of CLASRP-overexpressing CRC cells, resulting in direct blockade of cell growth. The expression levels of cleaved caspase 3 and cleaved caspase 8 were increased in CLASRP-overexpressing CRC cells treated with Clk inhibitors. CLASRP might serve as a promotional oncogene in CRC cells and be suppressed by Clk inhibitors through activation of caspase pathways.
Identifiants
pubmed: 37658940
doi: 10.1007/s10142-023-01208-8
pii: 10.1007/s10142-023-01208-8
pmc: PMC10474993
doi:
Substances chimiques
CLASRP protein, human
0
Serine-Arginine Splicing Factors
170974-22-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
290Informations de copyright
© 2023. The Author(s).
Références
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