Soonchunhyang Medical Science Research Institute, Cheonan, South Chungcheong 31151, Republic of Korea.
Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Cheonan, South Chungcheong 31151, Republic of Korea.
Mol Med Rep. 2018 Jun;17(6):8173-8179. doi: 10.3892/mmr.2018.8915. Epub 2018 Apr 23.
Loss of runt‑related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty‑five endometrial cancer tissues and two endometrial cancer cell lines (HEC1‑α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription‑polymerase chain reaction (RT‑PCR), methylation specific PCR (MS‑PCR), and immunohistochemical staining. The demethylating agent 5‑aza‑2'‑deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1‑α cell line by immunohistochemistry and RT‑PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1‑α cell line by MS‑PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1‑α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.
RUNX3 缺失已在多种癌症中报道，介导 RUNX3 表达缺失的机制之一是 DNA 甲基化。然而，RUNX3 表达及其 DNA 甲基化状态作为子宫内膜癌预后因素的作用仍不清楚。在本研究中，检测了 RUNX3 在子宫内膜癌组织和细胞系中的表达和启动子甲基化及其与子宫内膜癌预后的关系。研究了 55 例子宫内膜癌组织和 2 种子宫内膜癌细胞系（HEC1-α 和 Ishikawa）。采用逆转录-聚合酶链反应（RT-PCR）、甲基化特异性 PCR（MS-PCR）和免疫组织化学染色检测 RUNX3 的表达和启动子甲基化。使用去甲基化剂 5-氮杂-2'-脱氧胞苷（ADC）逆转 RUNX3 启动子的甲基化。免疫组织化学和 RT-PCR 分别观察到 50.9%（27/53）的子宫内膜癌组织和 HEC1-α 细胞系中 RUNX3 表达缺失。MS-PCR 观察到 62.2%（33/53）的子宫内膜癌组织、12.5%（1/8）的正常子宫内膜组织和 HEC1-α 细胞系中 RUNX3 启动子甲基化。肿瘤分级和分期与 RUNX3 表达缺失显著相关。用 ADC 处理可恢复 RUNX3 的表达，并导致 HEC1-α 细胞生长抑制。这些结果表明，甲基化可能在 RUNX3 沉默中起关键作用，RUNX3 表达缺失可能作为子宫内膜癌的预后标志物。
