NEAT1/miR-200b-3p/SMAD2 axis promotes progression of melanoma

• DOI: 10.18632/aging.103909
• Publication Date: 2020-11-18T05:05:27Z
• Authors: Wen-Jie Zhou; Hao-Yu Wang; Jie Zhang; Hai-Ying Dai; Zhi-Xian Yao; Zhong Zheng; Sun Meng-Yan; Ke Wu
• Keywords: 0303 health sciences; Epithelial-Mesenchymal Transition; Skin Neoplasms; Smad2 Protein; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Databases, Genetic; Humans; Neoplasm Invasiveness; RNA, Long Noncoding; Melanoma; Research Paper; Cell Proliferation; Signal Transduction

Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. Overexpression of miR-200b-3p significantly inhibited the proliferation and invasion of melanoma cells. According to bioinformatics analysis and sequencing data, we supposed that SMAD family member 2 (SMAD2) was the target gene and nuclear enriched abundant transcript 1 (NEAT1) was the upstream long non-coding RNA (lncRNA) of miR-200b-3p. These predictions were verified by western blotting and quantitative real-time reverse transcription PCR (RT-qPCR). Luciferase reporter assays revealed that NEAT1 up-regulated SMAD2 by directly sponging miR-200b-3p. In vitro and in vivo, we demonstrated that both NEAT1 and SMAD2 could promote the proliferation and invasion of melanoma cells, and these effects were reversed by up-regulating miR-200b-3p. In addition, NEAT1/miR-200b-3p/SMAD2 axis promoted melanoma progression by activating EMT signaling pathway and immune responses. Taken together, the NEAT1/miR-200b-3p/SMAD2 signaling pathway promotes melanoma via activation of EMT, cell invasion and is related with immune responses, which provides new insights into the molecular mechanisms and therapeutic targets for melanoma.