Department of Burn and Plastic Surgery, Chengdu Second People's Hospital, Chengdu, China.
Department of Burn and Plastic Surgery, the Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Exp Dermatol. 2021 Dec;30(12):1764-1774. doi: 10.1111/exd.14427. Epub 2021 Jul 12.
Melanoma is considered as the most common malignancy among skin cancers. The roles of many long non-coding RNAs (lncRNAs) have been clearly identified in multiple tumors. Nevertheless, lncRNA MSC antisense RNA 1 (MSC-AS1) has not been deeply investigated melanoma. In the present study, RT-qPCR and western blot analyses were used to measure the expression of RNAs and proteins. Functional and in vivo assays were implemented to detect the function of genes in melanoma. RNA pull-down, RIP and luciferase reporter assays were applied for determining interactions between RNA and protein molecules. It was observed that MSC-AS1 and lymphoid enhancer-binding factor 1 (LEF1) were remarkably up-regulated while microRNA-302a-3p (miR-302a-3p) down-regulated in melanoma cell lines. The silencing of MSC-AS1 hindered cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Furthermore, MSC-AS1 regulated LEF1 expression through sponging miR-302a-3p and recruiting insulin like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Eventually, LEF1 overexpression rescued cell progression impaired by MSC-AS1 knock-down. In summary, our research identified the MSC-AS1/miR-302a-3p/IGF2BP2/LEF1 axis in melanoma development, which indicated that MSC-AS1 is a potential biomarker in the treatment of melanoma.
黑色素瘤被认为是皮肤癌中最常见的恶性肿瘤。许多长链非编码 RNA(lncRNA)在多种肿瘤中的作用已被明确鉴定。然而,lncRNA MSC 反义 RNA 1(MSC-AS1)在黑色素瘤中的研究还不够深入。在本研究中,使用 RT-qPCR 和 Western blot 分析来测量 RNA 和蛋白质的表达。实施功能和体内实验来检测黑色素瘤中基因的功能。应用 RNA 下拉、RIP 和荧光素酶报告基因实验来确定 RNA 和蛋白质分子之间的相互作用。结果表明,MSC-AS1 和淋巴增强结合因子 1(LEF1)在黑色素瘤细胞系中显著上调,而 microRNA-302a-3p(miR-302a-3p)下调。MSC-AS1 的沉默在体外抑制细胞增殖、迁移和上皮间质转化(EMT),并在体内抑制肿瘤生长。此外,MSC-AS1 通过海绵吸附 miR-302a-3p 和募集胰岛素样生长因子 2mRNA 结合蛋白 2(IGF2BP2)来调节 LEF1 的表达。最终,LEF1 的过表达挽救了 MSC-AS1 敲低导致的细胞进展受损。总之,我们的研究鉴定了黑色素瘤发生发展中的 MSC-AS1/miR-302a-3p/IGF2BP2/LEF1 轴,表明 MSC-AS1 是治疗黑色素瘤的潜在生物标志物。