RUNX3 has an oncogenic role in head and neck cancer.
RUNX3 has an oncogenic role in head and neck cancer.
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DOI：
10.1371/journal.pone.0005892
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发表时间：
2009-06-12
期刊：
影响因子：
3.7
通讯作者：
Takata T
中科院分区：
文献类型：
--
作者：
Tsunematsu T;Kudo Y;Iizuka S;Ogawa I;Fujita T;Kurihara H;Abiko Y;Takata T
Runt-related transcription factor 3（RUNX 3）是一种肿瘤抑制因子，是转化生长因子β（TGF-β）诱导的肿瘤抑制途径的重要组成部分。令人惊讶的是，我们在我们的初步研究中发现，RUNX 3在头颈部鳞状细胞癌（HNSCC）组织（这是人类最常见的癌症类型之一）中的表达水平高于正常组织中的表达水平。因此，我们在此研究了RUNX 3在HNSCC中的致癌作用。在HNSCC中观察到RUNX 3的频繁表达及其与恶性行为的相关性。异位RUNX 3过表达促进细胞生长，抑制血清饥饿诱导的HNSCC细胞凋亡和化疗药物诱导的细胞凋亡。这些发现通过RUNX 3敲低得到证实。此外，RUNX 3过表达增强肿瘤球形成。RUNX 3的表达水平与HNSCC细胞的甲基化状态密切相关。此外，由于RUNX 3启动子在正常口腔上皮细胞中的甲基化，RUNX 3表达较低。我们的研究结果表明，i）RUNX 3在HNSCC中具有致癌作用，ii）在HNSCC中观察到的RUNX 3表达可能部分由癌症发展过程中的去甲基化引起，iii）RUNX 3表达可以是预测HNSCC中恶性行为和化疗药物作用的有用标志物。
Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of cancer and appears to be an important component of the transforming growth factor-beta (TGF-ß)-induced tumor suppression pathway. Surprisingly, we found that RUNX3 expression level in head and neck squamous cell carcinoma (HNSCC) tissues, which is one of the most common types of human cancer, was higher than that in normal tissues by a previously published microarray dataset in our preliminary study. Therefore, here we examined the oncogenic role of RUNX3 in HNSCC. Frequent RUNX3 expression and its correlation with malignant behavior were observed in HNSCC. Ectopic RUNX3 overexpression promoted cell growth and inhibited serum starvation-induced apoptosis and chemotherapeutic drug induced apoptosis in HNSCC cells. These findings were confirmed by RUNX3 knockdown. Moreover, RUNX3 overexpression enhanced tumorsphere formation. RUNX3 expression level was well correlated with the methylation status in HNSCC cells. Moreover, RUNX3 expression was low due to the methylation of its promoter in normal oral epithelial cells. Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can be a useful marker for predicting malignant behavior and the effect of chemotherapeutic drugs in HNSCC.
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