ABSTRACT

Breast cancer remains a general-threat event in the health of women. Currently, increasing records indicate that long non-coding RNA maternally expressed 3 (MEG3) plays a central role in breast cancer. The current research focused on the function of MEG3 in paclitaxel (PTX)-resistance and human breast cancer growth. Levels of MEG3, microRNA (miR)-4513, and phenazine biosynthesis-like domain-containing protein (PBLD) were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assays. 3-(4.5-dimethylghiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay was performed to examine the IC₅₀ of PTX and cell proliferation in breast cancer cells. In addition, cell apoptosis was determined utilizing flow cytometry. Transwell was conducted to assay cell migration and invasion in MCF-7 and MDA-MB-231 cells. The interaction between miR-4513 and MEG3 or PBLD was expounded via dual-luciferase reporter assay. Levels of MEG3 and PBLD were decreased, but miR-4513 level was triggered in breast cancer tissues and cell lines. Overexpression of MEG3 could reinforce cell apoptosis, impede proliferation, migration, invasion, and the IC50 of PTX in breast cancer cells. Moreover, the impact of miR-4513 inhibitor on cell progression and PTX-resistance was overturned by MEG3 deficiency. Interestingly, miR-4513 mimic could abolish the role of PBLD upregulation in cell behaviors and PTX-resistance in MCF-7 and MDA-MB-231 cells. Finally, the expression of PBLD was co-modulated by miR-4513 and MEG3 in vitro. MEG3/miR-4513/PBLD axis modulated PTX-resistance and the development of breast cancer cells, which might provide a promising therapeutic strategy for breast cancer.

摘要

乳腺癌仍然是女性健康的普遍威胁事件。目前，越来越多的记录表明，长链非编码 RNA 母源表达 3 (MEG3) 在乳腺癌中起着核心作用。目前的研究集中在 MEG3 在紫杉醇 (PTX) 耐药性和人类乳腺癌生长中的功能。使用定量实时聚合酶链反应 (qRT-PCR) 或蛋白质印迹分析法评估 MEG3、微小 RNA (miR)-4513 和吩嗪类生物合成结构域蛋白 (PBLD) 的水平。进行 3-(4.5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定以检查 IC ₅₀PTX 和乳腺癌细胞中的细胞增殖。此外，使用流式细胞术测定细胞凋亡。进行 Transwell 以测定 MCF-7 和 MDA-MB-231 细胞中的细胞迁移和侵袭。miR-4513 与 MEG3 或 PBLD 之间的相互作用通过双荧光素酶报告基因测定进行阐述。MEG3 和 PBLD 的水平降低，但 miR-4513 水平在乳腺癌组织和细胞系中被触发。MEG3的过表达可以增强细胞凋亡，阻碍乳腺癌细胞的增殖、迁移、侵袭和PTX的IC50。此外，miR-4513 抑制剂对细胞进展和 PTX 抗性的影响被 MEG3 缺陷所推翻。有趣的是，miR-4513 模拟物可以消除 PBLD 上调在 MCF-7 和 MDA-MB-231 细胞中的细胞行为和 PTX 抗性中的作用。最后，体外。MEG3/miR-4513/PBLD 轴调节 PTX 抗性和乳腺癌细胞的发展，这可能为乳腺癌提供一种有前景的治疗策略。