ABSTRACT

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.

摘要

长链非编码 RNA (lncRNA) FAM83H-AS1 最近被确定在许多人类癌症中具有致癌作用。但其在膀胱癌 (BCa) 发病机制中的作用和机制在很大程度上尚未得到研究。本研究旨在评估FAM83H-AS1在BCa细胞和相关机械分子的恶性行为和血管生成中的作用。与正常细胞相比，在 82 个 BCa 组织和 BCa 细胞系中发现 FAM83H-AS1 的高表达。T24 和 BK10 细胞中的 FAM83H-AS1 下调抑制了 BCa 细胞的活力、集落形成、迁移、侵袭和血管生成，并增加了细胞凋亡。发现 FAM83H-AS1 与转录因子 c-Myc 结合以激活 ULK3 表达。在 FAM83H-AS1 沉默的情况下，ULK3 的过表达被进一步引入 T24 和 BK10 细胞，这阻断了 FAM83H-AS1 下调对 BCa 细胞生长的抑制作用。Hedgehog 信号通路的活性被 FAM83H-AS1 抑制，而被 ULK3 恢复。Hedgehog 通路的抑制减少了 ULK3 促进的 BCa 细胞的恶性行为。这体外实验结果在体内重现。该研究证明 FAM83H-AS1 通过转录因子 c-Myc 上调 ULK3 表达并促进 BCa 的进展。