Min Xie, Huaiyuan Liang, Yuxuan Mao, Yuping Yao, Bingzhang Tian
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引用次数: 0
摘要
胆管癌（Colangiocarcinoma，CCA）是一种侵袭性癌症，对化疗或放疗反应不佳，因此需要新的治疗方法。表观遗传调控是可逆的，在癌症进展中起着重要作用。CBX3（HP1γ）是一种关键的异染色质蛋白，它通过与组蛋白H3赖氨酸9三甲基（H3K9me3）标记相互作用来调节基因表达。虽然 CBX3 与多种癌症的肿瘤进展有关，但它在 CCA 中的作用仍不清楚。这项研究发现，CBX3 和 H3K9me3 富集了 HLTF 启动子，HLTF 是一种参与染色质重塑和 DNA 修复的基因。在其他癌症中，HLTF 常因高甲基化而失活，这表明它具有抑制肿瘤的特性。消耗 CCA 细胞中的 CBX3 会提高 HLTF 的表达，从而减少增殖，而沉默 HLTF 则会逆转这种效应。此外，HLTF 的过表达抑制了 CBX3 激活的 PI3K-AKT 信号转导。这些发现表明，CBX3 通过抑制 HLTF 的表达促进了 CCA 的进展。
CBX3 Downregulates HLTF to Activate PI3K/AKT Signaling Promoting Cholangiocarcinoma.
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.
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