Silence of long non-coding RNA UCA1 inhibits hemangioma cells growth, migration and invasion by up-regulation of miR-200c.Life Sci. 2019 Jun 01; 226:33-46.LS
Human urothelial carcinoma associated 1 (UCA1) has been recognized as an oncogenic lncRNA in various cancers, except infantile hemangioma (IH). This study attempts to explore the functional role of lncRNA UCA1 in IH.
qRT-PCR was carried out to detect the expression of lncRNA UCA1 in human IH tissues. Two hemangioma cell lines (EOMA and HemECs) were transfected with shRNAs specific for lncRNA UCA1, or a plasmid for expression lncRNA UCA1. The expression of miR-200c in cell was suppressed or overexpressed by miRNA-mediated transfection. CCK-8 assay, flow cytometry, Transwell assay, and Western blot were performed to detect cell survival, migration and invasion.
LncRNA UCA1 was up-regulated in proliferating-phase hemangioma samples, as compared to involuting-phase. Silence of lncRNA UCA1 significantly reduced EOMA cells viability, migration and invasion, and induced apoptosis. These observations were coupled with the down-regulations of CyclinD1, CDK6 and CDK4, the cleavage of caspase-3 and caspase-9, as well as the decreased expression levels of MMP-9 and Vimentin. miR-200c was highly expressed in lncRNA UCA1 silenced-cells. Besides, the anti-tumor effects of lncRNA UCA1 silence towards EOMA cells were reversed by miR-200c suppression. Same effects of lncRNA UCA1 and miR-200c on HemECs cells were observed. Furthermore, silence of lncRNA UCA1 repressed mTOR, AMPK and Wnt/β-catenin signaling via a miR-200c-dependent fashion.
This study evidences that silence of lncRNA UCA1 inhibits hemangioma cells growth, migration and invasion possibly via its regulation on miR-200c expression and the activation of mTOR, AMPK and Wnt/β-catenin signaling pathways.