Runx2 (Runt-related transcription factor 2) is a key transcription factor which is associated with osteoblast differentiation and expressed in ER+ (estrogen receptor positive) human breast cancer cell lines. Runx2 also participates in mammary gland development. Deregulation of RNA Pol III genes (polymerase III-dependent genes) is tightly linked to tumor development, while Brf1 (TFIIB-related factor 1) specifically regulates these gene transcription. However, nothing is known about the effect of Runx2 on Brf1 expression and Pol III gene transcription. Expression of Runx2, Brf1 and Pol III genes from the samples of human breast cancer and cell culture model were determined by the assays of RT-qPCR, immunoblot, luciferase reporter activity, immunohistochemistry, chromatin immunoprecipitation and Immunofluorescence. High expression of Runx2 is observed in the cases of breast cancer. The patients of high Runx2 expression at early stages display longer survival period, whereas the cases of high Runx2 at advanced stages reveal faster recurrence. The identification of signaling pathway indicates that JNK1 and c-Jun mediate Runx2 transcription. Repression of Runx2 reduces Brf1 expression and Pol III gene transcription. Further analysis indicates that Runx2 is colocalized with Brf1 in nucleus of breast cancer tissue. Both Runx2 and Brf1 synergistically modulate Pol III gene transcription. These studies indicate that Brf1 overexpression is able to be used as an early diagnosis biomarker of breast cancer, while high Runx2 expression indicates long survival period and faster recurrence. Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer.

中文翻译：

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Runx2 介导酒精诱导的 Brf1 表达和 RNA Pol III 基因转录的意义。

Runx2（Runt 相关转录因子 2）是与成骨细胞分化相关并在 ER+（雌激素受体阳性）人乳腺癌细胞系中表达的关键转录因子。Runx2 还参与乳腺发育。RNA Pol III 基因（聚合酶 III 依赖性基因）的失调与肿瘤发展密切相关，而 Brf1（TFIIB 相关因子 1）特异性调节这些基因转录。然而，关于 Runx2 对 Brf1 表达和 Pol III 基因转录的影响，我们一无所知。通过 RT-qPCR、免疫印迹、荧光素酶报告基因活性、免疫组织化学、染色质免疫沉淀和免疫荧光测定来确定来自人类乳腺癌样品和细胞培养模型的 Runx2、Brf1 和 Pol III 基因的表达。在乳腺癌病例中观察到 Runx2 的高表达。早期Runx2高表达的患者生存期较长，而晚期Runx2高表达的患者复发较快。信号通路的鉴定表明JNK1和c-Jun介导了Runx2的转录。Runx2 的抑制降低了 Brf1 的表达和 Pol III 基因的转录。进一步分析表明，Runx2 与 Brf1 共定位在乳腺癌组织的细胞核中。Runx2 和 Brf1 都协同调节 Pol III 基因转录。这些研究表明，Brf1过表达可作为乳腺癌的早期诊断生物标志物，而Runx2高表达表明生存期长、复发快。