Abstract：
BACKGROUND: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.
METHODS: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.
RESULTS: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.
CONCLUSIONS: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.
METHODS: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.
RESULTS: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.
CONCLUSIONS: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.
摘要：
背景：舌鳞状细胞癌（TSCC）表现出淋巴结和远处转移的侵袭性生物学行为，这导致预后较差，并导致舌功能丧失或死亡。除了已知的调节因子和TSCC中细胞迁移的途径，发现控制肿瘤转移的关键开关很重要。
方法：在TSCC中分析了癌细胞迁移相关的转录和表观遗传特征，并鉴定了特定的超级增强子(SE)。通过分子功能和机制研究来研究TSCC转移中的关键开关。
结果：在TSCC中富集了伴随转录和表观遗传活性的Ameboidd型细胞迁移相关基因。同时,排序较高的SE相关基因在来自TCGATSCC队列的43个配对肿瘤样本和正常样本之间显示出显著差异.此外,在SE地区检测到关键基序，转录因子相关表达水平与TSCC生存状态显著相关。值得注意的是,BATF和ATF3通过切换与SE区的相互作用来调节变形虫型细胞迁移相关MMP14的表达。
结论：SE和相关关键基序转录调控肿瘤转移相关的MMP14，可能是TSCC的潜在治疗靶点。
方法：在TSCC中分析了癌细胞迁移相关的转录和表观遗传特征，并鉴定了特定的超级增强子(SE)。通过分子功能和机制研究来研究TSCC转移中的关键开关。
结果：在TSCC中富集了伴随转录和表观遗传活性的Ameboidd型细胞迁移相关基因。同时,排序较高的SE相关基因在来自TCGATSCC队列的43个配对肿瘤样本和正常样本之间显示出显著差异.此外,在SE地区检测到关键基序，转录因子相关表达水平与TSCC生存状态显著相关。值得注意的是,BATF和ATF3通过切换与SE区的相互作用来调节变形虫型细胞迁移相关MMP14的表达。
结论：SE和相关关键基序转录调控肿瘤转移相关的MMP14，可能是TSCC的潜在治疗靶点。
