Department of Traditional Chinese Medicine, The Second Hospital of Hengshui City, Hengshui City, Hebei Province, P.R. China.
Department of Dermatology, Harrison International Heping Hospital, Hengshui City, Hengshui City, Hebei Province, P.R. China.
Oncol Res. 2018 Jun 11;26(5):675-681. doi: 10.3727/096504017X14920318811730. Epub 2017 Apr 12.
Melanoma is an extremely aggressive malignant skin tumor with a high mortality. Various long noncoding RNAs (lncRNAs) have been reported to be associated with the oncogenesis of melanoma. The purposes of this study were to investigate the potential role of lncRNA PVT1 in melanoma progression and to explore its possible mechanisms. A total of 35 patients who were diagnosed with malignant melanoma were enrolled in this study. Expression of PVT1 was significantly upregulated in melanoma tissue and was associated with a poor prognosis. Loss-of-function experiments showed that PVT1 knockdown markedly suppressed the proliferation activity, induced cell cycle arrest at the G0/G1 phase, and enhanced the apoptosis of melanoma cell lines. Bioinformatics analysis and dual-luciferase reporter assay revealed that PVT1 directly bound to miR-26b, which had been verified to be a tumor suppressor in melanoma. Moreover, further functional rescue experiments revealed that PVT1 knockdown could observably reverse the tumor-promoting role of the miR-26b inhibitor. Overall, our study demonstrates the oncogenic role of PVT1 as a miR-26b sponge, possibly providing a novel therapeutic target for melanoma.
黑色素瘤是一种具有高死亡率的侵袭性恶性皮肤肿瘤。已有研究报道多种长链非编码 RNA(lncRNA)与黑色素瘤的发生有关。本研究旨在探讨 lncRNA PVT1 在黑色素瘤进展中的潜在作用及其可能的机制。共纳入 35 例诊断为恶性黑色素瘤的患者。结果显示,PVT1 在黑色素瘤组织中呈显著高表达,与不良预后相关。功能丧失实验表明,PVT1 敲低可显著抑制黑色素瘤细胞系的增殖活性,诱导细胞周期停滞于 G0/G1 期,并促进细胞凋亡。生物信息学分析和双荧光素酶报告基因实验显示,PVT1 可直接结合 miR-26b,而 miR-26b 已被证实是黑色素瘤中的一种肿瘤抑制因子。此外,进一步的功能恢复实验表明,PVT1 敲低可显著逆转 miR-26b 抑制剂的促瘤作用。综上所述,本研究表明 PVT1 作为 miR-26b 海绵的致癌作用,可能为黑色素瘤提供新的治疗靶点。