Ma Haiming, Liu Tao, Xu Yanhua, Wang Xinying, Wang Jin, Liu Xiaokang
Department of Oncology, Guangrao County People's Hospital, Dongying City, Shandong Province 257300, People's Republic of China.
Department of General Surgery, Guangrao County People's Hospital, Dongying City, Shandong Province 257300, People's Republic of China.
Onco Targets Ther. 2020 Dec 18;13:12987-12997. doi: 10.2147/OTT.S281962. eCollection 2020.
MiR-519d and miR-328-3p had tumor-regulatory properties in different cancers, but their combinatorial effects and potential common target in breast cancer had not been fully reported. This research targeted to study the underlying mechanism of how miR-519d and miR-328-3p cooperatively suppressed breast cancer.
MiR-519d and miR-328-3p expressions in breast cancer tissues and cells were assessed and Ki-67 expression was also checked. DLR assay was executed to verify whether Ki-67 was a common target of miR-519d and miR-328-3p. Western blot, flow cytometry, colony formation, wound healing and transwell assays were applied to examine the inhibitory roles of these two miRNAs on the malignant behaviors of breast cancer cells and the potential molecular mechanism.
Impeded miR-519d and miR-328-3p expressions and enhanced Ki-67 expression were detected in breast cancer tissues and cells. Ki-67 was confirmed as a target of these two miRNAs. MiR-519d and miR-328-3p hampered cell proliferation and blocked cell cycle via binding to Ki-67 and they also suppressed migration and invasion. The combinatorial effects of two miRNAs were much stronger than a single miRNA.
Our findings proved that miR-519d and miR-328-3p played combinatorial anti-cancer roles in breast cancer by directly targeting a common target Ki-67. Our study suggested that these two miRNAs might own the potential to become novel therapeutic biomarkers involved in the diagnosis and therapy of breast cancer.
MiR-519d和miR-328-3p在不同癌症中具有肿瘤调节特性,但其在乳腺癌中的联合作用及潜在共同靶点尚未完全报道。本研究旨在探讨miR-519d和miR-328-3p协同抑制乳腺癌的潜在机制。
评估乳腺癌组织和细胞中miR-519d和miR-328-3p的表达,并检测Ki-67的表达。进行双荧光素酶报告基因检测以验证Ki-67是否为miR-519d和miR-328-3p的共同靶点。应用蛋白质免疫印迹法、流式细胞术、集落形成实验、伤口愈合实验和Transwell实验来检测这两种微小RNA对乳腺癌细胞恶性行为的抑制作用及其潜在分子机制。
在乳腺癌组织和细胞中检测到miR-519d和miR-328-3p表达受阻,Ki-67表达增强。Ki-67被确认为这两种微小RNA的靶点。MiR-519d和miR-328-3p通过与Ki-67结合阻碍细胞增殖并阻断细胞周期,它们还抑制迁移和侵袭。两种微小RNA的联合作用比单一微小RNA强得多。
我们的研究结果证明,miR-519d和miR-328-3p通过直接靶向共同靶点Ki-67在乳腺癌中发挥联合抗癌作用。我们的研究表明,这两种微小RNA可能有潜力成为参与乳腺癌诊断和治疗的新型治疗生物标志物。