Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/β-catenin signaling pathway

• Published in: Molecular cancer 2018-01, Vol.17 (1), p.3-3
• Main Authors: Wang, Ze-You, Hu, Min, Dai, Min-Hui, Xiong, Jing, Zhang, Shuai, Wu, Han-Jiang, Zhang, Shan-Shan, Gong, Zhao-Jian
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Cell Cycle - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Cell Survival - genetics; Disease Models, Animal; Disease Progression; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Male; Mice; Middle Aged; Neoplasm Grading; Neoplasm Staging; RNA, Long Noncoding - genetics; Tongue Neoplasms - genetics; Tongue Neoplasms - metabolism; Tongue Neoplasms - mortality; Tongue Neoplasms - pathology; Wnt Signaling Pathway
• ISSN: 1476-4598
• DOI: 10.1186/s12943-017-0752-2

Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues. The correlation between AFAP1-AS1 and the clinicopathological features was evaluated using the chi-square test. The effects of AFAP1-AS1 on TSCC cells were determined via a CCK-8 assay, clone formation assay, flow cytometry, wound healing assay and transwell assay. Furthermore, the effect of AFAP1-AS1 knockdown on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, CAL-27 cells with AFAP1-AS1 knockdown were subcutaneously injected into nude mice to evaluate the effect of AFAP1-AS1 on tumor growth in vivo. In this study, we found that lncRNA AFAP1-AS1 was increased in TSCC tissues and that patients with high AFAP1-AS1 expression had a shorter overall survival. Short hairpin RNA (shRNA)-mediated AFAP1-AS1 knockdown significantly decreased the proliferation of TSCC cells. Furthermore, AFAP1-AS1 silencing partly inhibited cell migration and invasion. Inhibition of AFAP1-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of EMT-related genes (SLUG, SNAIL1, VIM, CADN, ZEB1, ZEB2, SMAD2 and TWIST1) in TSCC cells. In addition, CAL-27 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on tumorigenesis in vivo. Downregulation of AFAP1-AS1 suppressed tumor growth and inhibited the expression of EMT-related genes (SLUG, SNIAL1, VIM, ZEB1, NANOG, SMAD2, NESTIN and SOX2) in vivo. Taken together, our findings present a road map for targeting the newly identified lncRNA AFAP1-AS1 to suppress TSCC progression, and these results elucidate a novel potential therapeutic strategy for TSCC.