Han Xiaoting, Guo Xiaolong, Zhang Wenzhen, Cong Qiumei
Department of Breast Surgery, Weihai Central Hospital, Shandong 264400, People's Republic of China.
Department of Breast Surgery, Zibo Maternity and Child Health Hospital, Shandong 255020, People's Republic of China.
Onco Targets Ther. 2019 Jun 20;12:4813-4824. doi: 10.2147/OTT.S207593. eCollection 2019.
Numerous microRNAs (miRNAs) are aberrantly expressed in breast cancer, and the dysregulation of miRNAs may affect the aggressiveness of this cancer. Aberrant expression of miRNA-937 (miR-937) in gastric and lung cancers has been reported, which plays tumor-suppressive or oncogenic roles in carcinogenesis including cancer progression. Our purpose was to investigate the involvement of miR-937 in breast cancer progression. The expression profile of miR-937 in breast cancer was assessed by reverse-transcription quantitative PCR. Biological effects of miR-937 upregulation on the malignant characteristics of breast cancer cells were determined in a series of functional experiments. The direct target of miR-937 in breast cancer cells was also identified. Herein, the expression levels of miR-937 were notably lower in breast cancer, and its underexpression was significantly correlated with lymph node metastasis and TNM stage. Patients with breast cancer underexpressing miR-937 showed shorter overall survival than did patients with breast cancer overexpressing miR-937. Proliferation, migration, and invasiveness of breast cancer cells were evidently suppressed by miR-937 upregulation. In addition, ectopic miR-937 expression hindered breast cancer tumor growth in vivo. Forkhead box Q1 () mRNA was found to be a direct target of miR-937 in breast cancer. FOXQ1 turned out to be overexpressed in breast cancer tissues, and its overexpression negatively correlated with miR-937 expression. Moreover, silencing of FOXQ1 recapitulated the tumor-suppressive effects of miR-937 overexpression on breast cancer cells. Notably, FOXQ1 restoration abrogated the miR-937-mediated suppression of proliferation, migration, and invasiveness of breast cancer cells. These results collectively revealed that miR-937 acts as a tumor suppressor in breast cancer and restrains cancer progression by directly targeting mRNA. These data suggest that targeting of the novel miR-937-FOXQ1 axis is an attractive therapeutic method against breast cancer.
众多微小RNA（miRNA）在乳腺癌中表达异常，而miRNA的失调可能会影响这种癌症的侵袭性。已有报道称miRNA - 937（miR - 937）在胃癌和肺癌中表达异常，其在包括癌症进展在内的致癌过程中发挥肿瘤抑制或致癌作用。我们的目的是研究miR - 937在乳腺癌进展中的作用。通过逆转录定量PCR评估miR - 937在乳腺癌中的表达谱。在一系列功能实验中确定了miR - 937上调对乳腺癌细胞恶性特征的生物学效应。还鉴定了miR - 937在乳腺癌细胞中的直接靶点。在此，miR - 937的表达水平在乳腺癌中显著降低，其低表达与淋巴结转移和TNM分期显著相关。miR - 937低表达的乳腺癌患者的总生存期短于miR - 937高表达的乳腺癌患者。miR - 937上调明显抑制了乳腺癌细胞的增殖、迁移和侵袭。此外，异位表达miR - 937可在体内抑制乳腺癌肿瘤生长。发现叉头框Q1（FOXQ1）mRNA是miR - 937在乳腺癌中的直接靶点。结果表明FOXQ1在乳腺癌组织中过表达，其过表达与miR - 937表达呈负相关。此外，沉默FOXQ1可重现miR - 937过表达对乳腺癌细胞的肿瘤抑制作用。值得注意的是，恢复FOXQ1可消除miR - 937介导的对乳腺癌细胞增殖、迁移和侵袭的抑制作用。这些结果共同表明，miR - 937在乳腺癌中起肿瘤抑制作用，并通过直接靶向FOXQ1 mRNA抑制癌症进展。这些数据表明，靶向新的miR - 937 - FOXQ1轴是一种有吸引力的抗乳腺癌治疗方法。
