Promoting roles of long non-coding RNA FAM83H-AS1 in bladder cancer growth, metastasis, and angiogenesis through the c-Myc-mediated ULK3 upregulation.

Long non-coding RNA (lncRNA) FAM83H-AS1 has been recently identified with oncogenic roles in many human cancers. But its role in bladder cancer (BCa) pathogenesis and the mechanisms are largely unstudied. This study aims to evaluate the roles of FAM83H-AS1 in the malignant behaviors and the angiogenesis of BCa cells and the mechanical molecules involved. High expression of FAM83H-AS1 was found in 82 BCa tissues and in BCa cell lines compared to the normal ones. FAM83H-AS1 downregulation in T24 and BK10 cells inhibited viability, colony formation, migration, invasion, and angiogenesis of BCa cells and increased cell apoptosis. FAM83H-AS1 was found to bind to the transcription factor c-Myc to activate ULK3 expression. Overexpression of ULK3 was further introduced into T24 and BK10 cells in the presence of FAM83H-AS1 silencing, which blocked the inhibitory effects of FAM83H-AS1 downregulation on BCa cell growth. The activity of the Hedgehog signaling pathway was suppressed by FAM83H-AS1 while recovered by ULK3. Suppression of the Hedgehog pathway reduced the malignant behaviors of BCa cells promoted by ULK3. The in vitro experiment results were reproduced in vivo. This study evidenced that FAM83H-AS1 upregulates ULK3 expression through the transcription factor c-Myc and promotes the progression of BCa.