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CBX3 Downregulates HLTF to Activate PI3K/AKT Signaling Promoting Cholangiocarcinoma

Year: 2024

Type: article

Abstract: Cholangiocarcinoma (CCA) is an aggressive cancer with poor response to chemotherapy or radiation, necessitating novel therapeutic approaches. Epigenetic regulation, which is reversible, plays a significant role in cancer progression. CBX3 (HP1γ), a key heterochromatin protein, regulates gene expression by interacting with histone H3 lysine 9 trimethyl (H3K9me3) markers. While CBX3 is linked to tumor progression in various cancers, its role in CCA remains unclear. This study reveals that CBX3 and H3K9me3 enrich the HLTF promoter, a gene involved in chromatin remodeling and DNA repair. HLTF is often inactivated by hypermethylation in other cancers, suggesting tumor-suppressive properties. Depleting CBX3 in CCA cells elevates HLTF expression, reducing proliferation, while HLTF silencing reverses this effect. Furthermore, HLTF overexpression inhibits PI3K-AKT signaling activated by CBX3. These findings suggest CBX3 promotes CCA progression by suppressing HLTF expression.

Source: Advanced Biology

DOI: 10.1002/adbi.202400413

Authors: Min Xie, Huaiyuan Liang, Yuxuan Mao, Yuping Yao, Bingzhang Tian

Institutions: Hunan Normal University, Hunan Provincial People's Hospital, Central South University, Second Xiangya Hospital of Central South University, Xiangya Hospital Central South University

Language: English

Topic: Cholangiocarcinoma and Gallbladder Cancer Studies

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Central South University, Natural Science Foundation of Hunan Province, Fundamental Research Funds for the Central Universities