ZNF460-mediated upregulation of APCDD1L-DT promotes cholangiocarcinoma development by inhibiting the ubiquitin-mediated degradation of DVL2.

Autor: Gao X; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Zou X; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Guan C; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Sha X; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Liu S; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Zhang X; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Yang C; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China., Zhong X; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. hmuzhongxy@163.com., Jiang X; Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. xmjiang@hrbmu.edu.cn.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2024 Oct; Vol. 31 (10), pp. 1585-1597. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1038/s41417-024-00826-z
Abstrakt: Cholangiocarcinoma (CCA), known for its aggressive nature, poses a formidable challenge in the current medical landscape, particularly in targeted therapies. Against this backdrop, long non-coding RNAs (lncRNAs) have captured the attention of researchers. These unique RNAs are believed to play pivotal roles in various cancers, offering promising avenues for the development of more effective treatment strategies. Previous studies have substantiated the aberrant expression of the APCDD1L-DT in numerous human tumors, demonstrating its positive regulatory roles in disease progression. Nevertheless, the biological functions of APCDD1L-DT in CCA are still not fully understood. This study marks the inaugural documentation of APCDD1L-DT exhibiting aberrant expression in CCA specimen, establishing a close correlation with the TNM staging of tumor patients. Furthermore, suppressing APCDD1L-DT expression hinders both the viability and motility of tumor cells. Mechanistically, the abnormal activation of the transcription factor ZNF460 positively regulated APCDD1L-DT expression in CCA. This activation, in turn, propels the abnormal activation of the Wnt pathway, fostering tumor development by impeding the ubiquitin-mediated degradation of DVL2. Broadly speaking, this study provides auspicious perspectives for comprehending CCA and furnishes support for addressing this daunting malignancy.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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