Department of Hematology, Jingzhou Central Hospital, Jingzhou, Hubei 434020, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11691. Epub 2020 Nov 17.
MicroRNA (miR)‑140‑5p is associated with the growth and metastasis of various tumor cell types, yet its role in multiple myeloma (MM) remains unclear. Therefore, the present study aimed to investigate the regulatory effect of miR‑140‑5p on MM. Reverse transcription‑quantitative PCR analysis demonstrated that miR‑140‑5p was downregulated in MM cell lines, particularly in U266 and RPMI 8226 cells. A Cell Counting Kit‑8, wound healing and Transwell assays, as well as flow cytometry indicated that a miR‑140‑5p mimic could suppress cell viability, migration and invasion. In addition, the mimic promoted apoptosis of U266 and RPMI 8226 cells. Western blot data demonstrated that transfection with miR‑140‑5p mimic significantly reduced the expression levels of Ki‑67, cyclin D1, vimentin, Snail, matrix metalloproteinase (MMP)‑2 and MMP‑3. Moreover, as predicted by TargetScan7.2 and verified by luciferase activity assay, it was demonstrated that vascular endothelial growth factor A (VEGFA) was targeted by miR‑140‑5p. Further experiments indicated that VEGFA overexpression promoted cell viability, migration and invasion and suppressed apoptosis of MM cells, and that the miR‑140‑5p mimic partially reversed the effects of VEGFA overexpression. Therefore, miR‑140‑5p suppressed MM progression by targeting VEGFA. The present findings provide insight into potential therapeutic strategies for the treatment of MM.
微小 RNA(miR)-140-5p 与各种肿瘤细胞类型的生长和转移有关,但它在多发性骨髓瘤(MM)中的作用尚不清楚。因此,本研究旨在探讨 miR-140-5p 对 MM 的调控作用。逆转录定量 PCR 分析表明,miR-140-5p 在 MM 细胞系中下调,特别是在 U266 和 RPMI 8226 细胞中。细胞计数试剂盒-8 检测、划痕愈合和 Transwell 检测以及流式细胞术表明,miR-140-5p 模拟物可抑制细胞活力、迁移和侵袭。此外,模拟物可促进 U266 和 RPMI 8226 细胞的凋亡。Western blot 数据表明,转染 miR-140-5p 模拟物可显著降低 Ki-67、cyclin D1、波形蛋白、Snail、基质金属蛋白酶(MMP)-2 和 MMP-3 的表达水平。此外,通过 TargetScan7.2 预测并通过荧光素酶活性测定验证,血管内皮生长因子 A(VEGFA)是 miR-140-5p 的靶标。进一步的实验表明,VEGFA 过表达促进 MM 细胞的活力、迁移和侵袭,并抑制细胞凋亡,而 miR-140-5p 模拟物部分逆转了 VEGFA 过表达的作用。因此,miR-140-5p 通过靶向 VEGFA 抑制 MM 进展。本研究结果为 MM 的治疗策略提供了新的思路。