Department of General surgery, The Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China; Department of Biliary Tract Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai 200438, China.
Department of Biliary Tract Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai 200438, China.
Gene. 2019 Apr 30;694:102-110. doi: 10.1016/j.gene.2018.12.086. Epub 2019 Feb 1.
Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) contribute to tumorigenesis, progression and recurrence of various malignancies including Gallbladder carcinoma (GBC). Lnc-DILC is reported to be the tumor suppressor gene to play an important role in liver cancer stem cells (CSCs). However, the role of lnc-DILC in GBC remains to be elucidated. Herein, we show that lnc-DILC is upregulated in gallbladder CSCs and GBC patients' tissues. Knockdown of lnc-DILC attenuates the self-renewal, tumorigenicity, proliferation and metastasis of gallbladder CSCs. Mechanistically, lnc-DILC promotes gallbladder CSCs expansion via Wnt/β-catenin pathway. Special Wnt/β-catenin inhibitor FH535 diminishes the discrepancy of self-renewal, growth and metastasis between lnc-DILC interference GBC cells and their control cells. In conclusion, lnc-DILC drives gallbladder CSCs self-renewal, tumorigenicity, proliferation and metastasis by activating Wnt/β-catenin signaling, and may therefore prove to be a potential therapeutic target for GBC patients.
越来越多的证据表明，长非编码 RNA（lncRNA）参与了多种恶性肿瘤的发生、发展和复发，包括胆囊癌（GBC）。lnc-DILC 被报道为肿瘤抑制基因，在肝癌干细胞（CSC）中发挥重要作用。然而，lnc-DILC 在 GBC 中的作用仍有待阐明。本研究表明，lnc-DILC 在胆囊 CSC 和 GBC 患者组织中上调。lnc-DILC 的敲低可减弱胆囊 CSC 的自我更新、致瘤性、增殖和转移。机制上，lnc-DILC 通过 Wnt/β-catenin 通路促进胆囊 CSC 的扩增。特异性 Wnt/β-catenin 抑制剂 FH535 可减少 lnc-DILC 干扰 GBC 细胞及其对照细胞之间自我更新、生长和转移的差异。总之，lnc-DILC 通过激活 Wnt/β-catenin 信号通路驱动胆囊 CSC 的自我更新、致瘤性、增殖和转移，因此可能成为 GBC 患者的潜在治疗靶点。
