LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer.
LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer.
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DOI：
10.1038/s41419-018-1170-0
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发表时间：
2018-11-21
影响因子：
9
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Gong P;Qiao F;Wu H;Cui H;Li Y;Zheng Y;Zhou M;Fan H
越来越多的研究表明，长非编码RNA(LncRNAs)在肿瘤的发生、发展等生物学过程中发挥着重要作用。然而，目前对lncRNA UCA1在胃癌发生发展过程中的确切作用和调控机制知之甚少。在本研究中，我们发现UCA1在胃癌组织中异常升高，并且与淋巴结转移和TNM分期显著相关。在体内和体外，增强UCA1水平可促进GC细胞的迁移和侵袭。在胃癌中，UCA1表达减弱，细胞的迁移和侵袭能力减弱。然后，我们检测到与肿瘤转移相关的转录因子ZEB2在GC细胞中的表达水平受到UCA1的调控。MIR-203靶向并抑制TO ZEB2的表达。此外，我们还发现UCA1可以直接与miR-203相互作用，并导致miR-203靶向转录本ZEB2的释放。因此，我们揭示了UCA1在胃癌转移过程中通过海绵调控轴调控转移相关基因的新机制。我们的研究结果表明，UCA1通过介导海绵调节轴miR-203/ZEB2在转移性胃癌中发挥关键作用。探讨UCA1-miR-203-ZEB2轴的功能可能为肿瘤的生物学标记物和高选择性的抗GC治疗提供新的靶点。
Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that UCA1 was aberrantly elevated in gastric cancer tissues, and was significantly associated with lymph node metastasis and TNM stage. In vivo and in vitro, enforced UCA1 level promoted cell migration and invasion of GC cell. Depleted UCA1 expression level attenuated the ability of cell migration and invasion in GC. And then, we detected that expression level of ZEB2, a transcription factor related to tumor metastasis, was regulated by UCA1 in GC cells. miR-203 targets and suppresses to ZEB2 expression. Furthermore, we found that UCA1 could directly interact with miR-203 and lead to the release of miR-203-targeted transcripts ZEB2. Herein, we revealed the novel mechanism of UCA1 on regulating metastasis-related gene by sponge regulatory axis during GC metastasis. Our findings indicated that UCA1 plays a critical role in metastatic GC by mediating sponge regulatory axis miR-203/ZEB2. To explore function of UCA1-miR-203-ZEB2 axis may provide an informative biomarker of malignancy and a highly selective anti-GC therapeutic target.
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影响因子：
4.6
作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
通讯作者：
Huang Z
长链非编码 RNA SNHG20 通过表观遗传沉默 P21 表达来促进非小细胞肺癌细胞增殖和迁移。
影响因子：
9
作者：
Chen Z;Chen X;Chen P;Yu S;Nie F;Lu B;Zhang T;Zhou Y;Chen Q;Wei C;Wang W;Wang Z
通讯作者：
Wang Z
影响因子：
8
作者：
Bindels, S.;Mestdagt, M.;Gilles, C.
通讯作者：
Gilles, C.
影响因子：
12.3
作者：
Marín-Béjar O;Mas AM;González J;Martinez D;Athie A;Morales X;Galduroz M;Raimondi I;Grossi E;Guo S;Rouzaut A;Ulitsky I;Huarte M
通讯作者：
Huarte M
影响因子：
3.7
作者：
Duan, Xunhuang;Fu, Zhaojian;Luo, Rongcheng
通讯作者：
Luo, Rongcheng