Department of Oncology, RenMin Hospital of Wuhan University, Wuhan, China.
J Cell Physiol. 2019 Aug;234(10):18423-18431. doi: 10.1002/jcp.28478. Epub 2019 Apr 13.
Cancer stem cells (CSCs) have been recognized as the significant cause of tumor recurrence. Long noncoding RNAs (lncRNAs) are involved in various cancers, including human laryngeal cancer. So far the correlation between lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) and CSC-like properties in human laryngeal cancer remains barely known. In our current study, two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R) with different radio sensitivities were cultured. Interestingly, CSC-like phenotypes were much more enriched in Hep-2R cells. We found that DGCR5 was upregulated and microRNA-506 (miR-506) was downregulated in Hep-2R cells. In addition, silence of DGCR5 could inhibit the stemness and enhance the radiosensitivity of Hep-2R cells. Meanwhile, overexpression of miR-506 also suppressed the CSC-like traits and the radiosensitivity was increased significantly. In addition, miR-506 was predicted as target of DGCR5 and the correlation between them was validated in our study. Finally, we observed that Wnt pathway exerted a significant role in human laryngeal CSCs and DGCR5 inhibition could repress Wnt signaling activity by sponging miR-506. In vivo assays were performed and we found that DCGR5 depressed stemness of human laryngeal cancer cells through modulating miR-506 and Wnt signaling pathway. Taken these together, we reported that DGCR5 induced CSC-like properties by sponging miR-506 through activating Wnt in human laryngeal carcinoma cells.
癌症干细胞 (CSCs) 已被认为是肿瘤复发的重要原因。长链非编码 RNA (lncRNA) 参与多种癌症,包括人类喉癌。迄今为止,lncRNA DiGeorge 综合征关键区域基因 5 (DGCR5) 与人喉癌中的 CSC 样特性之间的相关性知之甚少。在我们目前的研究中,培养了两种具有不同放射敏感性的人喉鳞状细胞癌细胞系 (Hep-2 和 Hep-2R)。有趣的是,Hep-2R 细胞中 CSC 样表型更为丰富。我们发现 DGCR5 在 Hep-2R 细胞中上调,而 microRNA-506 (miR-506) 下调。此外,沉默 DGCR5 可以抑制 Hep-2R 细胞的干性并增强其放射敏感性。同时,过表达 miR-506 也抑制了 CSC 样特征,并且放射敏感性显著增加。此外,miR-506 被预测为 DGCR5 的靶标,并且在我们的研究中验证了它们之间的相关性。最后,我们观察到 Wnt 通路在人喉 CSCs 中发挥重要作用,DGCR5 通过海绵 miR-506 抑制 Wnt 信号活性。进行了体内实验,我们发现 DCGR5 通过调节 miR-506 和 Wnt 信号通路来抑制人喉癌细胞的干性。综上所述,我们报道了 DGCR5 通过激活 Wnt 海绵 miR-506 诱导人喉癌细胞中的 CSC 样特性。