LncRNA HOXA11-AS promotes migration and invasion through modulating miR-148a/WNT1/β-catenin pathway in gastric cancer

Tao Guo, Xiao Yuan, De-Feng Liu, Shi-Hao Peng,  A-Man Xu

Abstract:

Increasing researches have focused on the biological functions of long noncoding RNAs (lncRNAs) in human cancers. HOXA11-AS, a widely known lncRNA, has been confirmed to be involved in the progression of several cancers, including gastric cancer (GC). Whereas, the detailed mechanism of this lncRNA in GC remains to be further illuminated. The abundances of HOXA11-AS, miR-148a and WNT1 in GC tissues and cell lines were examined by qRT-PCR. Clinicopathological and Kaplan-Meier survival analyses were determined to explore the relationship between HOXA11-AS expression and outcomes of patients. Transwell assay was performed for the evaluation of cell migration and invasion. Bioinformatics, dual-luciferase reporter and RNA immunoprecipitation assays were employed to analyze the correlation between HOXA11-AS and miR-148a or miR-148a and WNT1. The protein levels of WNT1 and β-catenin were assessed by western blot assay. Results showed that HOXA11-AS and WNT1 expression levels were upregulated, while miR-148a level was downregulated in GC tissues and cell lines relative to matched controls. Elevated expression of HOXA11-AS was associated with increased tumor size, lymph node metastasis, advanced TNM stage, as well as reduced survival of GC patients. HOXA11-AS induced migration and invasion of GC cells through serving as a molecular sponge for miR-148a. Furthermore, miR-148a inactivated WNT1/β-catenin signaling pathway via directly targeting WNT1. HOXA11-AS increased WNT1/β-catenin pathway activity, which was abolished by miR-148a overexpression in GC cells. In conclusion, overexpression of HOXA11-AS contributed to migration and invasion of GC cells via activation of WNT1/β-catenin signaling pathway through repressing miR-148a, providing a prospective therapeutic target for GC.