State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
Theranostics. 2017 Oct 17;7(19):4836-4849. doi: 10.7150/thno.20942. eCollection 2017.
Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). However, the role of lncRNA in CRC liver metastasis remains unclear. a microarray was performed to identify the differentially expressed lncRNAs between CRC tissues with and without liver metastasis. Survival analysis was evaluated using the Kaplan-Meier method and assessed using the log-rank test. and assays were preformed to explore the biological effects of the differentially expressed lncRNA in CRC cells. the lncRNA UICLM (up-regulated in colorectal cancer liver metastasis) was significantly up-regulated in cases of CRC with liver metastasis. Moreover, UICLM expression was higher in CRC tissues than in normal tissues, and UICLM expression was associated with poor patient survival. Knockdown of UICLM inhibited CRC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and CRC stem cell formation as well as tumor growth and liver metastasis . Ectopic expression of UICLM promoted CRC cell proliferation and invasion. Mechanistic investigations revealed that UICLM induced its biological effects by regulating ZEB2, as the oncogenesis facilitated by UICLM was inhibited by ZEB2 depletion. Further study indicated that UICLM acted as a competing endogenous RNA (ceRNA) for miR-215 to regulate ZEB2 expression. taken together, our findings demonstrate how UICLM induces CRC liver metastasis and may offer a novel prognostic marker and therapeutic target for this disease.
长链非编码 RNA（lncRNA）参与多种肿瘤的病理学，包括结直肠癌（CRC）。然而，lncRNA 在 CRC 肝转移中的作用尚不清楚。通过微阵列分析鉴定出具有和不具有肝转移的 CRC 组织之间差异表达的 lncRNA。使用 Kaplan-Meier 方法进行生存分析，并使用对数秩检验进行评估。和 assays 被用来探索差异表达的 lncRNA 在 CRC 细胞中的生物学效应。lncRNA UICLM（结直肠癌肝转移中上调）在具有肝转移的 CRC 病例中显著上调。此外，UICLM 在 CRC 组织中的表达高于正常组织，并且 UICLM 的表达与患者生存不良相关。敲低 UICLM 抑制 CRC 细胞增殖、侵袭、上皮-间充质转化（EMT）和 CRC 干细胞形成以及肿瘤生长和肝转移。异位表达 UICLM 促进 CRC 细胞增殖和侵袭。机制研究表明，UICLM 通过调节 ZEB2 发挥其生物学效应，因为 UICLM 促进的致癌作用被 ZEB2 耗尽所抑制。进一步的研究表明，UICLM 作为 miR-215 的竞争性内源 RNA（ceRNA）来调节 ZEB2 表达。综上所述，我们的研究结果表明 UICLM 如何诱导 CRC 肝转移，并为该疾病提供新的预后标志物和治疗靶点。
