Cyclin A2 maintains colon homeostasis and is a prognostic factor in colorectal cancer.
Cell cycle
Colorectal cancer
Inflammation
Mouse models
Oncology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
15 02 2021
15 02 2021
Historique:
received:
10
07
2019
accepted:
09
12
2020
pubmed:
18
12
2020
medline:
21
9
2021
entrez:
17
12
2020
Statut:
ppublish
Résumé
To clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC), we generated mice deficient for cyclin A2 in colonic epithelial cells (CECs). Colons of these mice displayed architectural changes in the mucosa and signs of inflammation, as well as increased proliferation of CECs associated with the appearance of low- and high-grade dysplasias. The main initial events triggering those alterations in cyclin A2-deficient CECs appeared to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CECs promoted the development of dysplasia and adenocarcinomas in a murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein levels and found higher expression in tumors of patients with stage 1 or 2 CRC compared with those of patients with stage 3 or 4 CRC. A meta-analysis of 11 transcriptome data sets comprising 2239 primary CRC tumors revealed different expression levels of CCNA2 (the mRNA coding for cyclin A2) among the CRC tumor subtypes, with the highest expression detected in consensus molecular subtype 1 (CMS1) and the lowest in CMS4 tumors. Moreover, we found high expression of CCNA2 to be a new, independent prognosis factor for CRC tumors.
Identifiants
pubmed: 33332285
pii: 131517
doi: 10.1172/JCI131517
pmc: PMC7880422
doi:
pii:
Substances chimiques
CCNA2 protein, human
0
CCNA2 protein, mouse
0
Cyclin A2
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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