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BCL11B expression in hepatocellular carcinoma relates to chemosensitivity and clinical prognosis

Authors :
Hiroyuki Abe
Kenya Kamimura
Shujiro Okuda
Yu Watanabe
Jun Inoue
Yutaka Aoyagi
Toshifumi Wakai
Ryo Kominami
Shuji Terai
Source :
Cancer Medicine, Vol 12, Iss 14, Pp 15650-15663 (2023)
Publication Year :
2023
Publisher :
Wiley, 2023.

Abstract

Abstract Introduction B‐cell lymphoma/leukemia 11B (BCL11B) is a subunit of SWI/SNF chromatin remodeling complexes and functions in cell cycle regulation and apoptosis upon DNA replication stress and damages via transcription. Many malignancies were reported to exhibit changes in BCL11B gene expression; however, no study has focused on the relationship between BCL11B and hepatocellular carcinoma, which potentially exhibits DNA replication stress and damages upon its oncogenesis. Thus, in this study, we examined the molecular characterization of BCL11B expression in hepatocellular carcinoma. Methods and Results The cumulative progression‐free survival and overall survival were significantly longer in the clinical cases of BCL11B‐negative hepatocellular carcinoma than BCL11B‐positve cases. Microarray and real‐time PCR analyses in hepatocellular carcinoma cell lines indicated a correlation between BCL11B and GATA6, a gene reported to be correlated with oncogenic activities and resistance to anthracycline, which is often used for hepatocellular carcinoma chemotherapy. Consequently, BCL11B‐overexpressing cell lines exhibited resistance to anthracycline in cell growth assays and the resistance has been evidenced by the increased expression of BCL‐xL in cell lines. The results were supported by the analyses of human HCC samples showing the correlation between BCL11B and GATA6 expressions. Discussions and Conclusion Our results indicated that overexpression of BCL11B amplifies GATA6 expression in hepatocellular carcinoma in vitro and in vivo that leads to anti‐apoptotic signal activation, and induces resistance to chemotherapy, which influenced the postoperative prognosis.

Details

Language :
English
ISSN :
20457634
Volume :
12
Issue :
14
Database :
Directory of Open Access Journals
Journal :
Cancer Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.b28136d80b664370b096168307a180cc
Document Type :
article
Full Text :
https://doi.org/10.1002/cam4.6167