Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India.
Department of Surgical Oncology, Dr. Bhubaneswar Borooah Cancer Institute, Guwahati, Assam, 781016, India.
Mol Biol Rep. 2021 Jul;48(7):5399-5409. doi: 10.1007/s11033-021-06542-3. Epub 2021 Jul 15.
RUNX1T1 is extensively studied in the context of AML1-RUNX1T1 fusion protein in acute myeloid leukemia. Little is known about the function of RUNX1T1 itself, although data on its function and regulation have begun to emerge from clinical, and in vitro studies. It is a putative tumor suppressor, whose expression is altered in a variety of solid tumors. Recently, reduced expression of RUNX1T1 in triple-negative breast tumors, and its influence on prognosis was reported.
The Kaplan-Meier Plotter online tool was used to study the relationship between RUNX1T1 expression and survival of breast cancer patients. High RUNX1T1 expression was associated with longer overall survival (OS), relapse-free survival (RFS) and distant metastasis free survival (DMFS). RUNX1T1 expression positively and negatively influenced OS of patients with ERα-positive and ERα-negative breast tumors, respectively. It was also associated with prolonged RFS, and DMFS in tamoxifen-treated patients. Expression of RUNX1T1 and ERα mRNA was analyzed in 40 breast tumor samples, and breast cancer cell lines using RT-PCR. TCGA-BRCA data was mined to study the relationship between RUNX1T1 and ERα mRNA expression. ERα-positive breast tumors showed significantly higher RUNX1T1 mRNA expression compared to ERα-negative tumors. RUNX1T1 mRNA expression was analyzed by qRT-PCR in MCF-7 or T47D cells, which were treated with 17β-estradiol, or the ERα agonist PPT, alone or in combination with 4-hydroxytamoxifen. Effect of ERα knockdown was also investigated. Results indicate that estrogen downmodulated RUNX1T1 mRNA expression via ERα.
Higher expression of RUNX1T1 in breast tumors is associated with favourable prognosis. RUNX1T1 and ERα show co-ordinated expression in breast tumors, and breast cancer cell lines. Estrogen-ERα signalling downmodulates the expression of RUNX1T1 mRNA in ERα-positive breast cancer cells. In-depth investigations on the interaction between RUNX1T1 and ERα are warranted to unravel the role and relevance of RUNX1T1 in breast cancer.
RUNX1T1 在 AML1-RUNX1T1 融合蛋白的急性髓系白血病的背景下得到了广泛研究。虽然已经有一些关于其功能和调控的临床和体外研究数据，但对于 RUNX1T1 本身的功能却知之甚少。它是一种潜在的肿瘤抑制因子，其在各种实体瘤中的表达发生改变。最近，有研究报道三阴性乳腺癌中 RUNX1T1 的表达降低及其对预后的影响。
使用 Kaplan-Meier Plotter 在线工具研究 RUNX1T1 表达与乳腺癌患者生存之间的关系。高 RUNX1T1 表达与总生存期（OS）、无复发生存期（RFS）和无远处转移生存期（DMFS）延长相关。RUNX1T1 表达分别对 ERα 阳性和 ERα 阴性乳腺癌患者的 OS 产生正性和负性影响。它还与他莫昔芬治疗患者的 RFS 和 DMFS 延长相关。使用 RT-PCR 分析了 40 个乳腺癌样本和乳腺癌细胞系中 RUNX1T1 和 ERα mRNA 的表达。通过 TCGA-BRCA 数据挖掘研究 RUNX1T1 与 ERα mRNA 表达之间的关系。与 ERα 阴性肿瘤相比，ERα 阳性乳腺癌肿瘤中 RUNX1T1 mRNA 表达明显更高。用 17β-雌二醇或 ERα 激动剂 PPT 单独或与 4-羟基他莫昔芬联合处理 MCF-7 或 T47D 细胞，然后通过 qRT-PCR 分析 RUNX1T1 mRNA 表达。还研究了 ERα 敲低的效果。结果表明，雌激素通过 ERα 下调 RUNX1T1 mRNA 表达。
乳腺癌肿瘤中 RUNX1T1 表达较高与预后良好相关。RUNX1T1 和 ERα 在乳腺癌肿瘤和乳腺癌细胞系中表现出协调表达。雌激素-ERα 信号通过 ERα 下调 ERα 阳性乳腺癌细胞中 RUNX1T1 mRNA 的表达。需要对 RUNX1T1 和 ERα 之间的相互作用进行深入研究，以揭示 RUNX1T1 在乳腺癌中的作用和相关性。
