Cyclin A2 maintains colon homeostasis and is a prognostic factor in CRC.

Guo, Yuchen; Gabola, Monica; Lattanzio, Rossano; Paul, Conception; Pinet, Valérie; Tang, Ruizhi; Turali, Hulya; Bremond, Julie; Longobardi, Ciro; Maurizy, Chloé; Da Costa, Quentin; Finetti, Pascal; Boissière-Michot, Florence; Rivière, Benjamin; Lemmers, Céline; Garnier, Séverine; Bertucci, François; Zlobec, Inti; Chebli, Karim; Tazi, Jamal; ... (2021). Cyclin A2 maintains colon homeostasis and is a prognostic factor in CRC. The journal of clinical investigation, 131(4) American Society for Clinical Investigation 10.1172/JCI131517

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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 (CEC). Colons of those mice displayed architectural changes in the mucosa, and signs of inflammation as well as an increased proliferation of CEC associated with the appearance of low- and high-grade dysplasia. The main initial events triggering those alterations in cyclin A2 deficient CEC appear to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CEC promoted the development of dysplasia and adenocarcinomas in the murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein level and found higher expression in tumors of stage I and II patients compared to those of stage III and IV. A meta-analysis of 11 transcriptome datasets comprising 2,239 primary CRC tumors displayed different CCNA2 (the mRNA coding for cyclin A2) expression levels among the CRC tumor subtypes with highest in CMS1 and lowest in CMS4. Moreover, high expression of CCNA2 was found to be a new independent prognosis factor for CRC tumors.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit

UniBE Contributor:

Zlobec, Inti

ISSN:

1558-8238

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Inti Zlobec

Date Deposited:

11 Mar 2021 12:26

Last Modified:

11 Mar 2021 12:33

Publisher DOI:

10.1172/JCI131517

PubMed ID:

33332285

Uncontrolled Keywords:

Cell cycle Colorectal cancer Inflammation Mouse models Oncology

BORIS DOI:

10.48350/150071

URI:

https://boris.unibe.ch/id/eprint/150071

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