Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710069, P.R. China.
Oncol Rep. 2018 Oct;40(4):2056-2066. doi: 10.3892/or.2018.6633. Epub 2018 Aug 7.
The microRNAs (miRNAs/miRs) involved in the carcinogenesis and progression of malignant melanoma (MM) remain unclear. In the present study, miR‑590‑5p was identified to be upregulated in MM cells compared with human melanocytes using a reverse transcription‑quantitative polymerase chain reaction to screen established oncogenic and tumor suppressor miRNAs. miR‑590‑5p was demonstrated to inhibit the cell proliferation and tumor growth of MM cells in vitro and in vivo by performing Cell Counting Kit‑8 and tumour xenograft assays, respectively. In addition, flowcytometry assays indicated that miR‑590‑5p induced cell apoptosis and cell cycle arrest at the G1 stage in MM cells. Finally, luciferase assays and western blot analysis results confirmed that the transcriptional regulator Yes‑associated protein 1 (YAP1) is upregulated and inversely associated with miR‑590‑5p expression in MM cells, and is the direct target and functional mediator of miR‑590‑5p in MM. Altogether these results reveal the functional and mechanistic link between miR‑590‑5p and YAP1 in the progression of MM. Therefore, miR‑590‑5p is a potential therapeutic target in MM.
在黑色素瘤（MM）的发生和进展中涉及的 microRNAs（miRNAs/miRs）仍不清楚。在本研究中，通过逆转录-定量聚合酶链反应筛选已建立的致癌和肿瘤抑制 miRNA，发现与人类黑素细胞相比，MM 细胞中 miR-590-5p 上调。通过细胞计数试剂盒-8 和肿瘤异种移植测定，分别在体外和体内证明 miR-590-5p 抑制 MM 细胞的增殖和肿瘤生长。此外，流式细胞术检测表明 miR-590-5p 诱导 MM 细胞凋亡和细胞周期停滞在 G1 期。最后，荧光素酶测定和 Western blot 分析结果证实转录调节剂 Yes 相关蛋白 1（YAP1）在 MM 细胞中上调，并与 miR-590-5p 表达呈负相关，是 MM 中 miR-590-5p 的直接靶标和功能介质。总之，这些结果揭示了 miR-590-5p 在 MM 进展中的功能和机制联系。因此，miR-590-5p 是 MM 的潜在治疗靶点。
