Overexpression of lncRNA WWTR1-AS1 associates with tumor aggressiveness and unfavorable survival in head-neck squamous cell carcinoma.

Abstract

Long noncoding RNAs (lncRNAs) have been recognized as novel biomarkers and therapeutic targets in human cancer including head-neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the expression of a novel lncRNA WW domain containing transcription regulator 1 antisense RNA 1 (WWTR1-AS1) as well as its clinical significance and biological roles in HNSCC. The expression level of endogenous WWTR1-AS1 in primary HNSCC and paired adjacent nontumor mucosa was evaluated by quantitative reverse-transcription polymerase chain reaction. The correlations were assessed between WWTR1-AS1 expression and clinical data such as clinicopathological parameters and patient survival. Further, the molecular mechanisms of WWTR1-AS1 underlying HNSCC progression were detected by loss-of-function assay in vitro and bioinformatics analysis. Aberrant overexpression of WWTR1-AS1 in HNSCC samples showed a significant correlation between its higher expression levels and larger tumor size, cervical node metastasis, and poor prognosis. WWTR1-AS1 knockdown mediated by antisense oligonucleotide markedly inhibited cell proliferation, migration, invasion, tumorsphere formation as well as apoptosis resistance probably by modulating WWTR1 messenger RNA (mRNA) stability in HNSCC cells. Bioinformatics analysis revealed that WWTR1-AS1 expression positively correlated with WWTR1 expression in TCGA-HNSCC data sets. Together, our data provide evidence that aberrant upregulation of WWTR1-AS1 associates with malignant features and unfavorable prognosis in HNSCC, highlighting that WWTR1-AS1 might be a potential oncogenic lncRNA during HNSCC progression.