General Department, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, No. 181 Han Yu Road, Shapingba District, Chongqing 400030, China.
General Department, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, No. 181 Han Yu Road, Shapingba District, Chongqing 400030, China.
Gene. 2019 Aug 20;710:39-47. doi: 10.1016/j.gene.2019.05.043. Epub 2019 May 23.
Dysregulation of microRNAs (miRNAs) have been reported to contribute to malignant progression in melanoma. However, the roles and mechanisms of several miRNAs in melanoma remain poorly understood. In our study, we showed that miR-10b was significantly up-regulated in melanoma tissues and cell lines, and was associated with overall survival of melanoma patients. Inhibition of miR-10b dramatically suppressed melanoma cell proliferation, migration and invasion in vitro and inhibited tumor growth in vivo. Moreover, we defined ITCH as a direct and functional downstream target of miR-10b, and showed that there was an inverse correlation between the expression of ITCH and miR-10b on melanoma tissues. Down-regulation of ITCH partially attenuated the inhibitory effects of miR-10b inhibition on melanoma cell proliferation, migration and invasion. Furthermore，we found that miR-10b exerted its effects on melanoma by regulating the Wnt/β-catenin pathway. Taken together, our results demonstrated that miR-10b was an important epigenetic modifier, promoting melanoma progression through regulating ITCH/Wnt/β-catenin pathway. These results offer a new strategy for epigenetic cancer therapy.
miRNAs 的失调已被报道有助于黑色素瘤的恶性进展。然而，几种 miRNA 在黑色素瘤中的作用和机制仍知之甚少。在我们的研究中，我们表明 miR-10b 在黑色素瘤组织和细胞系中显著上调，并与黑色素瘤患者的总生存率相关。抑制 miR-10b 可显著抑制黑色素瘤细胞在体外的增殖、迁移和侵袭，并抑制体内肿瘤生长。此外，我们将 ITCH 定义为 miR-10b 的直接和功能下游靶标，并表明在黑色素瘤组织中 ITCH 和 miR-10b 的表达呈负相关。下调 ITCH 可部分减弱 miR-10b 抑制对黑色素瘤细胞增殖、迁移和侵袭的抑制作用。此外，我们发现 miR-10b 通过调节 Wnt/β-catenin 通路对黑色素瘤发挥作用。总之，我们的研究结果表明，miR-10b 是一种重要的表观遗传修饰物，通过调节 ITCH/Wnt/β-catenin 通路促进黑色素瘤的进展。这些结果为表观遗传癌症治疗提供了一种新策略。
