Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Soochow University, Jiangsu, China.
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Jiangsu, China.
Cancer Gene Ther. 2022 Mar;29(3-4):341-357. doi: 10.1038/s41417-021-00313-9. Epub 2021 Mar 5.
Studies have confirmed the relationship between dysregulated long noncoding RNAs and melanoma pathogenesis. However, the regulatory functions of long intergenic non-protein coding RNA 1291 (LINC01291) in melanoma remain unknown. Therefore, we evaluated LINC01291 expression in melanoma and explored its roles in regulating tumor behaviors. Further, the molecular events via which LINC01291 affects melanoma cells were investigated. LINC01291 expression in melanoma cells was analyzed using The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction. Functional assays, including the Cell Counting Kit-8 assay, colony formation assay, flow cytometry, cell migration and invasion assays, and tumor xenograft models, were used to examine LINC01291's role in melanoma cells. Additionally, bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, and western blotting were conducted to determine the tumor-promoting mechanism of LINC01291. LINC01291 was upregulated in melanoma tissues and cell lines. Following LINC01291 knockdown, cell proliferation, colony formation, migration, and invasion were diminished, whereas apoptosis was enhanced and the cell cycle was arrested at G0/G1. In addition, loss of LINC01291 decreased the chemoresistance of melanoma cells to cisplatin. Furthermore, LINC01291 interference inhibited melanoma tumor growth in vivo. Mechanistically, LINC01291 functions as a competing endogenous RNA by sponging microRNA-625-5p (miR-625-5p) in melanoma cells and maintaining insulin-like growth factor 1 receptor (IGF-1R) expression. Rescue experiments revealed that the roles induced by LINC01291 depletion in melanoma cells could be reversed by suppressing miR-625-5p or overexpressing IGF-1R. Our study identified the LINC01291/miR-625-5p/IGF-1R competing endogenous RNA pathway in melanoma cells, which may represent a novel diagnostic biomarker and an effective therapeutic target for melanoma.
研究已经证实失调的长非编码 RNA 与黑色素瘤发病机制之间存在关联。然而，长链非编码 RNA 1291（LINC01291）在黑色素瘤中的调控功能仍不清楚。因此，我们评估了黑色素瘤中 LINC01291 的表达，并探索了其调节肿瘤行为的作用。此外，还研究了 LINC01291 影响黑色素瘤细胞的分子事件。使用癌症基因组图谱数据库和实时定量聚合酶链反应分析黑色素瘤细胞中的 LINC01291 表达。使用细胞计数试剂盒-8 测定法、集落形成测定法、流式细胞术、细胞迁移和侵袭测定法以及肿瘤异种移植模型等功能测定法来检查 LINC01291 在黑色素瘤细胞中的作用。此外，进行生物信息学分析、RNA 免疫沉淀、荧光素酶报告基因测定和 Western blot 分析以确定 LINC01291 的促瘤机制。LINC01291 在黑色素瘤组织和细胞系中上调。敲低 LINC01291 后，细胞增殖、集落形成、迁移和侵袭减少，而凋亡增强，细胞周期停滞在 G0/G1 期。此外，LINC01291 的缺失降低了黑色素瘤细胞对顺铂的化疗耐药性。此外，LINC01291 干扰抑制了体内黑色素瘤肿瘤的生长。从机制上讲，LINC01291 在黑色素瘤细胞中作为竞争内源性 RNA 发挥作用，通过海绵吸附 microRNA-625-5p（miR-625-5p）并维持胰岛素样生长因子 1 受体（IGF-1R）的表达。挽救实验表明，通过抑制 miR-625-5p 或过表达 IGF-1R 可以逆转 LINC01291 耗尽在黑色素瘤细胞中诱导的作用。我们的研究确定了黑色素瘤细胞中的 LINC01291/miR-625-5p/IGF-1R 竞争内源性 RNA 通路，这可能代表一种新的诊断生物标志物和黑色素瘤的有效治疗靶点。
