Department of Urology, The First Affiliated Hospital of Bengbu Medical College , Bengbu, Anhui, P.R. China.
Cell Cycle. 2020 Dec;19(24):3546-3562. doi: 10.1080/15384101.2020.1850971. Epub 2020 Dec 8.
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 experiment results were reproduced . This study evidenced that FAM83H-AS1 upregulates ULK3 expression through the transcription factor c-Myc and promotes the progression of BCa.
长链非编码 RNA（lncRNA）FAM83H-AS1 最近被发现在许多人类癌症中具有致癌作用。但其在膀胱癌（BCa）发病机制中的作用及其机制在很大程度上尚未得到研究。本研究旨在评估 FAM83H-AS1 在膀胱癌细胞恶性行为和血管生成中的作用及其涉及的机械分子。与正常组织相比，82 例膀胱癌组织和膀胱癌细胞系中 FAM83H-AS1 的表达水平较高。在 T24 和 BK10 细胞中下调 FAM83H-AS1 可抑制膀胱癌细胞的活力、集落形成、迁移、侵袭和血管生成，并增加细胞凋亡。发现 FAM83H-AS1 与转录因子 c-Myc 结合，激活 ULK3 表达。在 FAM83H-AS1 沉默的情况下，进一步将 ULK3 过表达引入 T24 和 BK10 细胞中，阻断 FAM83H-AS1 下调对膀胱癌细胞生长的抑制作用。FAM83H-AS1 抑制 Hedgehog 信号通路的活性，而 ULK3 恢复其活性。抑制 Hedgehog 通路可降低 ULK3 促进的膀胱癌细胞的恶性行为。实验结果得到重现。本研究证明 FAM83H-AS1 通过转录因子 c-Myc 上调 ULK3 表达，促进膀胱癌的进展。
