Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression.
Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression.
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长非编码RNA UICLM通过作为microRNA-215的ceRNA调节ZEB2表达促进结直肠癌肝转移
作者：
Chen DL;Lu YX;Zhang JX;Wei XL;Wang F;Zeng ZL;Pan ZZ;Yuan YF;Wang FH;Pelicano H;Chiao PJ;Huang P;Xie D;Li YH;Ju HQ;Xu RH
长非编码RNA (lncRNA) 参与多种肿瘤的病理学，包括结直肠癌(CRC)。然而，lncRNA在CRC肝转移中的作用仍不清楚。方法：采用微阵列技术鉴定有肝转移和无肝转移的CRC组织之间差异表达的lncRNA。使用 Kaplan-Meier 方法评估生存分析并使用对数秩检验进行评估。进行体外和体内测定以探索CRC细胞中差异表达的lncRNA的生物学效应。结果：lncRNA UICLM（在结直肠癌肝转移中上调）在结直肠癌肝转移病例中显着上调。此外，UICLM在CRC组织中的表达高于正常组织，并且UICLM表达与患者生存率差相关。 UICLM的敲低在体外抑制CRC细胞增殖、侵袭、上皮间质转化（EMT）和CRC干细胞形成，在体内抑制肿瘤生长和肝转移。 UICLM的异位表达促进CRC细胞增殖和侵袭。机制研究表明，UICLM 通过调节 ZEB2 诱导其生物学效应，因为 UICLM 促进的肿瘤发生被 ZEB2 耗竭所抑制。进一步研究表明UICLM作为miR-215的竞争性内源RNA（ceRNA）来调节ZEB2表达。结论：综上所述，我们的研究结果证明了 UICLM 如何诱导 CRC 肝转移，并可能为该疾病提供新的预后标志物和治疗靶点。
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. Methods: 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. In vitro and in vivo assays were preformed to explore the biological effects of the differentially expressed lncRNA in CRC cells. Results: 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 in vitro as well as tumor growth and liver metastasis in vivo. 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. Conclusions: taken together, our findings demonstrate how UICLM induces CRC liver metastasis and may offer a novel prognostic marker and therapeutic target for this disease.
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影响因子：
4.7
作者：
Chen DL;Wang DS;Wu WJ;Zeng ZL;Luo HY;Qiu MZ;Ren C;Zhang DS;Wang ZQ;Wang FH;Li YH;Kang TB;Xu RH
通讯作者：
Xu RH
DOI：
10.1073/pnas.1503370112
发表时间：
2015-03-31
影响因子：
11.1
作者：
Jones, Matthew F.;Hara, Toshifumi;Lal, Ashish
通讯作者：
Lal, Ashish
影响因子：
3.4
作者：
Goldstein DA;Zeichner SB;Bartnik CM;Neustadter E;Flowers CR
通讯作者：
Flowers CR
长链非编码RNA：预测肿瘤侵袭和转移的潜在新生物标志物
影响因子：
37.3
作者：
Jiang C;Li X;Zhao H;Liu H
通讯作者：
Liu H
影响因子：
8
作者：
Li, X.;Roslan, S.;Khew-Goodall, Y.
通讯作者：
Khew-Goodall, Y.