Chemotherapy resistance is the major cause of nasopharyngeal carcinoma (NPC) treatment failure. Tripartite motif-containing protein (TRIM) family members play important roles in tumor development and chemotherapy failure. Here, based on a screening analysis of 71 TRIM family members by qRT-PCR, we first confirmed that the TRIM11 levels were significantly higher in drug-resistant NPC cells than in non-drug-resistant NPC cells, and high TRIM11 expression predicted poor overall survival (OS) and progression-free survival (PFS). N(6)-Methyladenosine (m6A) was highly enriched in TRIM11 in NPC drug-resistant cells and enhanced its RNA stability. TRIM11 enhanced the multidrug resistance in NPC by inhibiting apoptosis in vitro and promoting cisplatin (DDP) resistance in vivo. TRIM11 associated with Daple and promoted Daple ubiquitin-mediated degradation in a p62-selective autophagic manner, further upregulating β-catenin expression to induce ABCC9 expression by directly binding to the ABCC9 promoter. TRIM11 may regulate NPC drug resistance by positively modulating the Daple/β-catenin/ABCC9 signaling pathway. Thus, TRIM11 may be a potential diagnostic marker and therapeutic target for chemoresistant NPC.

中文翻译：

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TRIM11 通过 Daple 的 p62 选择性自噬降解激活 β-catenin/ABCC9 轴，促进鼻咽癌的化疗耐药。

化疗耐药是鼻咽癌（NPC）治疗失败的主要原因。三方基序蛋白 (TRIM) 家族成员在肿瘤发展和化疗失败中起重要作用。在这里，基于 qRT-PCR 对 71 个 TRIM 家族成员的筛选分析，我们首先证实，耐药 NPC 细胞中的 TRIM11 水平显着高于非耐药 NPC 细胞，高 TRIM11 表达预示着整体较差生存期（OS）和无进展生存期（PFS）。N(6)-甲基腺苷 (m6A) 在 NPC 耐药细胞中的 TRIM11 中高度富集，并增强了其 RNA 稳定性。TRIM11 通过在体外抑制细胞凋亡和在体内促进顺铂 (DDP) 耐药性来增强 NPC 的多药耐药性。TRIM11 与 Daple 相关并以 p62 选择性自噬方式促进 Daple 泛素介导的降解，进一步上调 β-catenin 表达以通过直接结合 ABCC9 启动子来诱导 ABCC9 表达。TRIM11 可能通过正向调节 Daple/β-catenin/ABCC9 信号通路来调节 NPC 耐药性。因此，TRIM11 可能是化疗耐药 NPC 的潜在诊断标志物和治疗靶点。