Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma

• Published in: Medical science monitor 2018-03, Vol.24, p.1547-1559
• Main Authors: Long, Jianwen, Menggen, Qiqige, Wuren, Qimige, Shi, Quan, Pi, Xianming
• Format: Article
• Language: English
• Subjects: Adult; Animals; Apoptosis - genetics; Base Sequence; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Cycle Checkpoints - genetics; Cell Line, Tumor; Cell Proliferation - genetics; Down-Regulation - genetics; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Lab/In Vitro Research; Male; Melanoma - genetics; Melanoma - pathology; Melanoma, Cutaneous Malignant; Membrane Proteins; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasm Metastasis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-Binding Proteins; Signal Transduction - genetics; Skin Neoplasms - genetics; Skin Neoplasms - pathology
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/MSM.906616

BACKGROUND Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers. The function of lncRNA TUG1 on growth of melanoma was investigated in this study. MATERIAL AND METHODS The TUG1 and miR-129-5p expression were examined via qRT-PCR. The protein expression was investigated by Western blotting assay. Luciferase reporter assay was used to assess if lncRNA TUG1 can bind to miR-129-5p and if miR-129-5p can target AEG1 mRNA. CCK-8 and apoptosis assay were used to detect cell growth and apoptosis. The metastasis of melanoma cells was detected by wound-healing and Transwell assays. The effects of TUG1 on growth of melanoma in vivo and cell chemoresistance were investigated via xenograft animal experiment and CCK-8 assay. RESULTS The expression of TUG1 and AEG1 was elevated and the miR-129-5p level was decreased in melanoma specimens and cell lines. Downregulation of either TUG1 or AEG1 suppressed cell growth and metastasis. miR-129-5p can bind directly to AEG1 and TUG1 can directly sponge miR-129-5p. Inhibition of TUG1 expression suppressed the expression of Bcl-2, MMP-9, and cyclin D1, and raised the level of cleaved caspase3 by modulating AEG1 level in melanoma cells. Inhibition of TUG1 reduced the growth of tumors in vivo and improved the chemosensitivity of A375 cells to cisplatin and 5-FU. CONCLUSIONS Reduction of TUG1 level suppressed cell growth and metastasis by regulating AEG1 expression mediated by targeting miR-129-5p. Suppression of lnc TUG1 may be a promising therapeutic strategy in the treatment of malignant melanoma.