Zhao Lifen, Feng Xiaobin, Song Xiaobo, Zhou Huimin, Zhao Yongfu, Cheng Lei, Jia Li
College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Oncol Rep. 2016 Aug;36(2):1007-15. doi: 10.3892/or.2016.4882. Epub 2016 Jun 16.
Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR‑493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR‑493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer.
乳腺癌是女性癌症相关死亡的主要原因。研究发现，岩藻糖基化改变与乳腺癌的发生和转移密切相关。微小RNA（miRNA）是细胞增殖和转移的重要调节因子，在乳腺癌中已观察到miRNA表达异常。本研究旨在评估乳腺癌中岩藻糖基转移酶IV（FUT4）和miR-493-5p的水平，并研究它们之间的关系。在本研究中，我们展示了FUT4和miR-493-5p在29例临床乳腺癌组织、配对的相邻组织样本以及两种乳腺癌细胞系（MCF-7和MDA-MB-231）中的差异表达谱。简而言之，FUT4表达水平的改变影响了MCF-7和MDA-MB-231细胞的侵袭活性和致瘤性。进一步研究表明，miR-493-5p在乳腺癌细胞侵袭和致瘤性中起抑制作用。此外，miR-493-5p的表达水平在mRNA和蛋白质水平上均与FUT4的表达水平呈负相关。荧光素酶报告基因检测证实，miR-493-5p与FUT4的3'非翻译区（3'-UTR）结合，并抑制乳腺癌细胞中FUT4的表达。综上所述，我们的数据表明FUT4可能在乳腺癌治疗中具有潜在作用，并且miR-493-5p是通过靶向FUT4调控乳腺癌细胞侵袭性和致瘤性的新型调节因子。miR-493-5p/FUT4通路在乳腺癌治疗中具有潜在应用价值。
