Deng Jiabin, Li Yinqiu, Song Jiaqian, Zhu Fei
Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu, Bengbu, Anhui 233000, P.R. China.
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Exp Ther Med. 2022 Jul 28;24(3):599. doi: 10.3892/etm.2022.11535. eCollection 2022 Sep.
Melanoma is the most prevalent malignancy of cutaneous carcinomas. Taurine-upregulated gene 1 (TUG1), a lncRNA, is a pivotal regulator of cutaneous malignancies. The present study aimed to investigate the impact and possible mechanisms of action of TUG1 behind the progression of melanomas. Reverse transcription-quantitative PCR was conducted to detect the expression levels of TUG1, microRNA (miR)-145-5p and SOX2 in melanoma tissues and cell lines. Cell Counting Kit-8 (CCK-8) assays were performed to measure the proliferative ability of melanoma cells and transwell assays were used to examine the migration and invasion of melanoma cells. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were utilized to identify the interactions among TUG1, miR-145-5p and SOX2. Western blotting and immunohistochemical assays were performed to determine the expression profile of SOX2. The impact of TUG1 on melanoma tumorigenesis was assessed using tumorigenicity assays. TUG1 expression levels were elevated in melanoma tumor tissues and cell lines. Reduced TUG1 expression levels significantly inhibited the proliferative, migratory and invasive abilities of melanoma cells. The expression levels of miR-145-5p were decreased in melanoma tumor tissues and cell lines. TUG1 directly targeted miR-145-5p and downregulated miR-145-5p. Upregulation of TUG1 counteracted the promotion of the proliferative, migratory and invasive abilities of melanoma cells induced by the overexpression of miR-145-5p. SOX2 was a target of miR-145-5p and its expression was negatively regulated by miR-145-5p, while positively regulated by TUG1. TUG1 regulated SOX2 expression through sponging miR-145-5p. Silencing of TUG1 also inhibited melanoma tumorigenesis in mice. In conclusion, the TUG1/miR-145-5p/SOX2 axis regulated the migration and invasion of melanoma cells.
黑色素瘤是皮肤癌中最常见的恶性肿瘤。牛磺酸上调基因1（TUG1）是一种长链非编码RNA（lncRNA），是皮肤恶性肿瘤的关键调节因子。本研究旨在探讨TUG1在黑色素瘤进展背后的影响及可能的作用机制。采用逆转录定量PCR检测黑色素瘤组织和细胞系中TUG1、微小RNA（miR）-145-5p和SOX2的表达水平。进行细胞计数试剂盒-8（CCK-8）试验以测量黑色素瘤细胞的增殖能力，并使用Transwell试验检测黑色素瘤细胞的迁移和侵袭能力。利用双荧光素酶报告基因和RNA免疫沉淀（RIP）试验来确定TUG1、miR-145-5p和SOX2之间的相互作用。进行蛋白质免疫印迹和免疫组织化学试验以确定SOX2的表达谱。使用致瘤性试验评估TUG1对黑色素瘤肿瘤发生的影响。TUG1在黑色素瘤肿瘤组织和细胞系中的表达水平升高。降低TUG1表达水平可显著抑制黑色素瘤细胞的增殖、迁移和侵袭能力。黑色素瘤肿瘤组织和细胞系中miR-145-5p的表达水平降低。TUG1直接靶向miR-145-5p并下调miR-145-5p。TUG1的上调抵消了miR-145-5p过表达对黑色素瘤细胞增殖、迁移和侵袭能力的促进作用。SOX2是miR-145-5p的靶标，其表达受miR-145-5p负调控，而受TUG1正调控。TUG1通过海绵吸附miR-145-5p来调节SOX2表达。沉默TUG1也可抑制小鼠黑色素瘤的肿瘤发生。总之，TUG1/miR-145-5p/SOX2轴调节黑色素瘤细胞的迁移和侵袭。
