Zhang Guangjing, Ai Dongfang, Yang Xiufang, Ji Shanshan, Wang Zhengxiang, Feng Shijun
Department of Dermatology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
Oncotarget. 2017 Oct 26;8(57):97361-97370. doi: 10.18632/oncotarget.22125. eCollection 2017 Nov 14.
Accumulating evidence showed that aberrant miRNAs expression was involved in initiation and progression of melanoma. However, the investigation of different miRNAs in melanoma remain attractive. In this research, we demonstrated that miR-610 expression was decreased in melanoma tissues and cell lines. The clinical data showed that the reduced miR-610 expression was obviously associated with adverse prognostic characteristics. Furthermore, our results suggested that miR-610 had a function of prognostic indicator for 5-year predicted-survival of melanoma patients. The ectopic overexpression of miR-610 suppressed cell proliferation, cell cycle progression and promoted apoptosis while miR-610 knockdown reversed the effect and . Additionally, miR-610 could modulate LRP6 by directly interacting to its 3'-UTR. In clinical samples of melanoma, miR-610 inversely correlated with LRP6. The biological function of miR-610 on melanoma cells was abrogated by alternation of LRP6 expression. In summary, our research indexed that miR-610 had a function of tumor suppressor in regulating the proliferation, cell cycle and apoptosis of melanoma via targeting LRP6. Hence, it may represent a novel potential therapeutic target and prognostic marker for melanoma.
越来越多的证据表明,异常的miRNAs表达与黑色素瘤的发生和发展有关。然而,对黑色素瘤中不同miRNAs的研究仍然具有吸引力。在本研究中,我们证明miR-610在黑色素瘤组织和细胞系中的表达降低。临床数据表明,miR-610表达降低明显与不良预后特征相关。此外,我们的结果表明,miR-610对黑色素瘤患者5年预测生存率具有预后指标功能。miR-610的异位过表达抑制细胞增殖、细胞周期进程并促进凋亡,而miR-610敲低则逆转了这种作用。此外,miR-610可通过直接与其3'-UTR相互作用来调节LRP6。在黑色素瘤临床样本中,miR-610与LRP6呈负相关。LRP6表达的改变消除了miR-610对黑色素瘤细胞的生物学功能。总之,我们的研究表明,miR-610通过靶向LRP6在调节黑色素瘤的增殖、细胞周期和凋亡方面具有肿瘤抑制功能。因此,它可能代表黑色素瘤一种新的潜在治疗靶点和预后标志物。