Bladder Cancer Progression Is Suppressed Through the Heart and Neural Crest Derivatives Expressed 2-Antisense RNA 1/microRNA-93-5p/Defective in Cullin Neddylation 1 Domain Containing 3 Axis.

Abstract

MicroRNAs (miRNAs) are critical in progression of bladder cancer (BCa). miRNA-93-5p is increased in cancers and is positively correlated with an unfavorable prognosis. But its effects on BCa remain rarely understood. This investigation aimed to dig out miRNA-93-5p affecting biological behaviors of BCa. In this research, mRNA and protein expression in cancer cells were assessed via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell Counting Kit-8 (CCK-8), colony formation, scratch healing, and transwell assays were utilized to analyze cancer cell viability, colony-forming, migration, and invasion, respectively. Bioinformatics analysis predicted upstream regulatory genes and downstream target genes of miRNA-93-5p, with the targeting relationship being verified through a dual-luciferase assay. The BCa xenograft model in nude mice further investigated the effect of miRNA-93-5p and AND2-AS1 on tumor size and quality, and validated the relationship between HAND2-AS1/miRNA-93-5p/DCUN1D3. Our results displayed that miRNA-93-5p was increased in BCa cell lines. Knockdown miRNA-93-5p constrained BCa cell malignant phenotypes. HAND2-AS1 targeted miRNA-93-5p, thus restraining malignant progression of BCa cells. DCUN1D3 was found downstream of miRNA-93-5p. miRNA-93-5p modulated proliferation, migration, and invasion of BCa cells by targeting DCUN1D3. In vivo experiments disclosed that forced expression of lncRNA HAND2-AS1, and inhibited miRNA-93-5p regressed tumor growth. Meanwhile, the same as the results of cell experiments, the expression of miRNA-93-5p was downregulated, and DCUN1D3 expression was advanced in tumor tissues. To conclude, lncRNA HAND2-AS1 exerted anti-tumor effects and regulated BCa cell proliferation, invasion, and migration by targeting miRNA-93-5p/DCUN1D3.