Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Hum Pathol. 2018 Jul;77:121-129. doi: 10.1016/j.humpath.2018.04.002. Epub 2018 Apr 22.
Advanced-stage breast cancer patients comprise a smaller proportion of breast cancer patients than do early stage patients and are more likely to experience a poor outcome. Understanding the underlying molecular mechanisms and identifying new biomarkers for treatment in this subgroup of patients is paramount. With the aim of identifying microRNAs that are regulated in advanced-stage breast cancer, we found lower expression of miR-26b, a member of the miR-26 family, in inflammatory breast cancer and noninflammatory locally advanced breast cancer tissue than in normal breast tissue, by quantitative real-time polymerase chain reaction and in situ hybridization. Quantitative real-time polymerase chain reaction (but not in situ hybridization) also revealed lower miR-26b expression in inflammatory breast cancer than in noninflammatory locally advanced breast cancer. Furthermore, lower expression of miR-26b was correlated with shorter distant metastasis-free survival and overall survival in univariate analysis, and with shorter overall survival in multivariate analysis. The expression of miRNA-26b was inversely associated with EZH2 protein expression in several breast cancer cell lines, and overexpression and knockdown of miR-26b caused corresponding changes in EZH2 expression. Our study shows that miR-26b may regulate EZH2 expression in breast cancer and may be useful as a therapeutic target for inflammatory breast cancer and noninflammatory locally advanced breast cancer.
晚期乳腺癌患者在乳腺癌患者中所占比例低于早期患者，且更有可能出现不良预后。了解这一亚组患者的潜在分子机制并确定新的治疗标志物至关重要。为了鉴定在晚期乳腺癌中受调控的 microRNAs，我们通过实时定量聚合酶链反应和原位杂交发现，与正常乳腺组织相比，炎症性乳腺癌和非炎症性局部晚期乳腺癌组织中 miR-26 家族的成员 miR-26b 的表达水平较低。实时定量聚合酶链反应（而非原位杂交）还显示，炎症性乳腺癌中 miR-26b 的表达水平低于非炎症性局部晚期乳腺癌。此外，在单变量分析中，miR-26b 表达水平较低与无远处转移生存时间和总生存时间较短相关，在多变量分析中，与总生存时间较短相关。miR-26b 的表达与几种乳腺癌细胞系中的 EZH2 蛋白表达呈负相关，miR-26b 的过表达和敲低导致 EZH2 表达相应改变。我们的研究表明，miR-26b 可能在乳腺癌中调节 EZH2 的表达，可作为炎症性乳腺癌和非炎症性局部晚期乳腺癌的治疗靶点。
