DDX11-AS1exacerbates bladder cancer progression by enhancing CDK6 expression via suppressing miR-499b-5p

Bladder Cancer
19/05/2020

Li Q, et al. Biomed Pharmacother 2020.

ABSTRACT

PURPOSE: We investigated DDX11-AS1 effects on bladder cancer (BLCA) progression to identify a new potential therapeutic target for BLCA.

METHODS: BLCA cases (n = 108) were enrolled. SW780 and J82 cells were transfected. Cell counting kit-8 (CCK-8) assay, wound healing assay and transwell migration assay was conducted. Cell cycle and apoptosis was detected by flow cytometry. Luciferase reporter assay was performed. DDX11-AS1, miR-499b-5p and CDK6 mRNA expression in tissues/cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). In vivo experiment was performed using nude mice. CDK6 and Ki67 proteins expression in cells and xenograft tumors were researched by Western blot and immunohistochemistry.

RESULTS: Overexpressed DDX11-AS1 in BLCA was associated with poor outcome of patients. Compared with siCtrl group, SW780 and J82 cells of siDDX11-AS1 group had lower OD450 value (P < 0.01), less cells in S phase, more apoptosis cells (P < 0.05), higher relative wound width (P < 0.05) and less invasive cell number (P < 0.01). DDX11-AS1 promoted CDK6 expression via inhibiting miR-499b-5p. Compared with oe-DDX11-AS1 group, SW780 cells of oe-DDX11-AS1 + miR-499b-5p mimic group and oe-DDX11-AS1 + siCDK6 group had lower OD450 value (P < 0.01), less cells in S phrase, more apoptosis cells (P < 0.01), higher relative wound width (P < 0.05) and less invasive cell numbers (P < 0.01). DDX11-AS1 knockdown inhibited SW780 cells growth in vivo and suppressed CDK6 and Ki67 expression in xenograft tumors.

CONCLUSION: DDX11-AS1 exacerbates BLCA progression by enhancing CDK6 expression via suppressing miR-499b-5p.