Long noncoding RNA DLX6-AS1 promotes cell growth and invasiveness in bladder cancer via modulating the miR-223-HSP90B1 axis

Abstract

ABSTRACT Long noncoding RNA (lncRNA) regulate many biological processes ranging from tumorigenesis to cancer metastasis. MicroRNA-223 (miR-223) acts as a novel tumor suppressor in bladder cancer (BC), however its target genes involved in BC, the molecular mechanisms governing its expression remain largely unknown. Both gain-of-function and loss of function experiments were performed to investigate the role of miR-223 in BC cells. The effects of miR-223 on BC progression were assessed using in vivo subcutaneous xenografts. The luciferase reporter assays were utilized to confirm the putative miR-223-binding site in the 3′-UTR of oncogene HSP90B1. The luciferase reporter assays and RNA immunoprecipitation assays were used to analyze the association between miR-223 and lncRNA DXL6-AS1 in BC cells. The expression of miR-223 was remarkably decreased in BC samples and BC cells. High miR-223 expression was correlated with favorable patient survival. BC cell growth in vivo was delayed by miR-223 overexpression. HSP90B1 was a direct target of miR-223 in BC cells, and the suppression of BC cell growth and invasion induced by miR-223 could be rescued by overexpression of HSP90B1. Moreover, lncRNA DXL6-AS1 was upregulated in BC tissues and functioned as a sponge for miR-223 and reduced its expression in BC cells, thereby enhancing cell proliferation and invasion. Forced expression of miR-223 could reverse the oncogenic effects of DXL6-AS1 on BC cell proliferation and invasion. Our study suggested that DLX6-AS1-mediated silencing of miR-223 promotes BC progression through the upregulation of HSP90B1.