Abstract 985: Downregulation of long noncoding RNA TINCR promotes invasion and metastasis and predicts poor prognosis in tongue squamous cell carcinoma

Abstract

Abstract Background and aim: Recently long non-coding RNAs (lncRNAs) have emerged as new gene regulators involving in a number of developmental and tumorigenic processes. However, few lncRNAs have been well characterized in tongue squamous cell carcinoma (TSCC). The aim of this study is to determine whether lncRNAs play a role in TSCC progression. Methods: The expression profiles of lncRNAs and protein-coding genes in TSCC tissues and paired adjacent non-tumor tissues from 10 patients were compared by using lncRNA microarrays. TSCC-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Levels of these differentially expressed lncRNAs were verified in TSCC tissues (n = 45) using Quantitative real-time PCR (qRT-PCR) and further confirmed in another patient cohort (n = 103) by in situ hybridization (ISH). The effects of lncRNA on tumor cell invasion and migration were assessed by silencing or overexpressing the lncRNA in vitro. Results: A total of 815 lncRNAs and 1783 protein-coding genes were differentially expressed between TSCC tissues and paired adjacent non-tumor tissues. WGCNA showed that one of the co-expression networks was significantly enriched for biological process that was relevant to epithelial cell differentiation, among which, TINCR was significantly down-regulated. Both PCR and ISH analyses validated that the down-regulation of TINCR in tumor tissues compared with controls. The expression level of TINCR was associated with tumor size, differentiation, cervical lymph node metastasis status, clinical stage and outcomes in patients with TSCC.Patients with TINCR low expression had a reduced overall survival. COX regression analysis showed that TINCR can be served as an independent prognostic factor for patients with TSCC. More, ectopic transfection of TINCR dramatically suppressed cell invasion and migration in vitro. On the contrary, knockdown of TINCR led to p63 upregulation, and enhanced cell invasion and migration. Conclusion: Our study suggests that downregulation of TINCR plays a role in TSCC progression, at least partially, by regulating epithelial differentiation-associated genes. Citation Format: Zehang Zhuang, Cheng Wang, Nan Xie, Yue Wu, Jinsong Hou, Xiqiang Liu, Hongzhang Huang. Downregulation of long noncoding RNA TINCR promotes invasion and metastasis and predicts poor prognosis in tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 985.