文章：

RP11-705C15.3/miR-145-5p/NRAS/MAPK信号轴对恶性黑色素瘤的调控

Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis 

原文发布日期：2020-12-14 

英文摘要：

Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in melanoma. We identified RP11-705C15.3, a regulator of miR-145-5p, as an oncogenic lncRNA in melanoma. RP11-705C15.3 competitively bound miR-145-5p, relieved the repressive roles of miR-145-5p on its target NRAS, upregulated NRAS expression, and activated MAPK signaling. In vitro functional assays revealed that ectopic expression of RP11-705C15.3 promoted melanoma cell proliferation, inhibited apoptosis, and promoted migration and invasion. Silencing of RP11-705C15.3 repressed melanoma cell proliferation, induced apoptosis, and repressed migration and invasion. Notably, the roles of RP11-705C15.3 in melanoma cell proliferation, apoptosis, migration and invasion are reversed by miR-145-5p overexpression. In vivo functional assays revealed that RP11-705C15.3 promoted melanoma tumor growth and metastasis, which were also reversed by miR-145-5p overexpression. Furthermore, we investigated the expression of RP11-705C15.3 in clinical melanoma tissues and found that RP11-705C15.3 was increased in melanoma tissues. High expression of RP11-705C15.3 was positively correlated with thickness, ulceration, metastasis, and inferior overall survival. Taken together, our findings suggest RP11-705C15.3 as a novel oncogene in melanoma, and highlight that the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis may be potential therapeutic targets for melanoma. 

摘要翻译： 

黑色素瘤是一种常见的致命性皮肤癌。解析驱动黑色素瘤恶性化的分子机制可能揭示潜在治疗靶点。我们既往研究发现miR-145-5p在黑色素瘤中具有重要肿瘤抑制功能。本研究进一步探讨长链非编码RNA（lncRNA）在黑色素瘤中的作用。我们发现RP11-705C15.3作为miR-145-5p的调控因子，在黑色素瘤中发挥致癌lncRNA功能。RP11-705C15.3通过竞争性结合miR-145-5p，解除miR-145-5p对其靶基因NRAS的抑制作用，上调NRAS表达并激活MAPK信号通路。体外功能实验表明：异位表达RP11-705C15.3可促进黑色素瘤细胞增殖、抑制凋亡、增强迁移和侵袭能力；而沉默RP11-705C15.3则抑制细胞增殖、诱导凋亡、减弱迁移和侵袭能力。值得注意的是，RP11-705C15.3对黑色素瘤细胞增殖、凋亡、迁移和侵袭的调控作用均可被miR-145-5p过表达所逆转。体内实验证实RP11-705C15.3能促进黑色素瘤肿瘤生长和转移，该效应同样可被miR-145-5p过表达逆转。此外，我们在临床黑色素瘤组织中发现RP11-705C15.3表达显著上调，其高表达与肿瘤厚度增加、溃疡形成、转移发生及不良总生存率呈正相关。本研究首次揭示RP11-705C15.3作为黑色素瘤新型致癌基因，并强调RP11-705C15.3/miR-145-5p/NRAS/MAPK信号轴可能成为黑色素瘤的潜在治疗靶点。

原文链接：

Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis