Departments of Breast Surgery, Chaoyang Hospital, Capital Medical University, Bejing, China.
Departments of General Surgery, New Century Women's and Children's Hospital, Beijing, China.
J Gene Med. 2020 Sep;22(9):e3168. doi: 10.1002/jgm.3168. Epub 2020 Aug 23.
The present study aimed to explore the functions and molecular mechanisms of miR-511 in breast cancer.
A quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-511 levels in breast cancer tissues; a chi-squared test was used to analyze the relationship between miR-511 expression level and pathological parameters of breast cancer patients; the proliferation of breast cancer cell lines MDA-MB-231 and MCF-7 was determined by the cell counting kit-8 (CCK-8) assay; migration was determined by scratch wound healing assay and transwell assay; TargetScan was used to predict the binding site between the 3'-untranslated region (3'-UTR) of fibroblast growth factor 4 (FGF4) and miR-511; and qRT-PCR, western blot and a luciferase reporter gene assay were conducted to further validate the targeting relationship between miR-511 and FGF4.
The expression level of miR-511 was lower in breast cancer tissues than that in adjacent normal tissues. Low expression of miR-511 was associated with larger tumor size, lymph node metastasis and short survival time. In vitro experiments showed that miR-511 modulated the proliferation and metastasis of breast cancer cells. It was also confirmed that miR-511 directly targeted 3'-UTR of FGF4 and reduced its expression, and FGF4 overexpression reversed the effect of miR-511 on the malignant phenotypes of breast cancer cells.
The results obtained in the present study demonstrate that miR-511 inhibits breast cancer proliferation and metastasis by down-regulating FGF4 expression, which may be helpful in the development of new treatment strategies for breast cancer.
本研究旨在探讨 miR-511 在乳腺癌中的功能和分子机制。
采用实时定量聚合酶链反应（qRT-PCR）检测乳腺癌组织中 miR-511 的水平；采用卡方检验分析 miR-511 表达水平与乳腺癌患者病理参数之间的关系；采用细胞计数试剂盒-8（CCK-8）检测乳腺癌细胞系 MDA-MB-231 和 MCF-7 的增殖；划痕愈合实验和 Transwell 实验检测迁移；TargetScan 预测成纤维细胞生长因子 4（FGF4）3'非翻译区（3'-UTR）与 miR-511 的结合位点；采用 qRT-PCR、western blot 和荧光素酶报告基因实验进一步验证 miR-511 与 FGF4 之间的靶向关系。
miR-511 在乳腺癌组织中的表达水平低于相邻正常组织。miR-511 低表达与肿瘤体积较大、淋巴结转移和生存时间短有关。体外实验表明，miR-511 调节乳腺癌细胞的增殖和转移。还证实 miR-511 可直接靶向 FGF4 的 3'-UTR，降低其表达，而过表达 FGF4 可逆转 miR-511 对乳腺癌细胞恶性表型的影响。
本研究结果表明，miR-511 通过下调 FGF4 表达抑制乳腺癌的增殖和转移，这可能有助于开发新的乳腺癌治疗策略。
