文章：

增强子劫持驱动FAM20C表达促进甲状腺乳头状癌进展

Enhancer hijacking drives FAM20C expression to promote papillary thyroid cancer progression 

原文发布日期：2025-06-30 

英文摘要：

Papillary thyroid cancer (PTC) is the most common endocrine cancer, with a good prognosis in most cases. However, aggressive PTC can metastasise or reoccur and become refractory disease. Therefore, it’s urgent to uncover new biomarkers for aggressive PTC. Accumulating evidence suggests that aberrant enhancers and targeted gene transcription drive the progression of PTC. To identify the cancer-specific enhancers and their downstream genes in PTC, we profiled the transcriptomes (RNA-seq) and enhancer-based epigenomic reorganisation (ChIP-seq) of cancer tissues and matched normal tissues from three PTC patients. Importantly, six candidate genes (RHBDF1, FAM20C, PHLDA2, TMPRSS6, LAD1, and BGN) were identified to be consistently upregulated by enhancers in PTC and correlated with prognosis. Further experiments verified the function of enhancers governing FAM20C in regulating PTC tumorigenesis, thereby unveiling a FAM20C-governed oncogenic mechanism for suppressing two cytokines (TNF-α and TGF-β) in PTC. Additionally, we demonstrated that a FAM20C inhibitor (3r) suppressed the proliferation and invasion of thyroid cancer cells in vitro and vivo. Moreover, FAM20C is driven by KLF12 through its enhancer. Collectively, our study uncovers the potential correlations between the aberrant activation of cancer-specific enhancers and PTC tumorigenesis and identifies FAM20C as a novel target for PTC. 

摘要翻译：

甲状腺乳头状癌（PTC）是最常见的内分泌系统癌症，多数患者预后良好。然而，侵袭性PTC可能发生转移或复发，进而发展为难治性疾病。因此，亟需揭示侵袭性PTC的新型生物标志物。越来越多的证据表明，异常增强子及其靶向基因转录驱动了PTC的进展。为识别PTC中癌症特异性增强子及其下游基因，我们通过转录组（RNA-seq）和基于增强子的表观基因组重组（ChIP-seq）技术，对三例PTC患者的癌组织及配对正常组织进行了分析。重要的是，研究发现六个候选基因（RHBDF1、FAM20C、PHLDA2、TMPRSS6、LAD1和BGN）在PTC中受增强子持续上调且与预后相关。进一步实验验证了调控FAM20C的增强子在PTC肿瘤发生中的功能，从而揭示了FAM20C通过抑制两种细胞因子（TNF-α和TGF-β）的致癌机制。此外，我们证明FAM20C抑制剂（3r）在体外和体内均能抑制甲状腺癌细胞的增殖与侵袭。值得注意的是，FAM20C受KLF12通过其增强子驱动。总体而言，本研究揭示了癌症特异性增强子异常激活与PTC肿瘤发生之间的潜在关联，并确定FAM20C作为PTC治疗的新靶点。

原文链接：

Enhancer hijacking drives FAM20C expression to promote papillary thyroid cancer progression