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长链非编码 RNA UCA1 通过诱导胃癌中的 miR-203/ZEB2 轴促进肿瘤转移。

LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer.

机构信息

Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, China.

School of Life Science, Southeast University, Nanjing, China.

出版信息

Cell Death Dis. 2018 Nov 21;9(12):1158. doi: 10.1038/s41419-018-1170-0.

Abstract

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.

摘要

越来越多的研究表明,长非编码 RNA(lncRNA)在包括癌症发生和进展在内的生物学过程中发挥着重要作用。然而,lncRNA UCA1 在胃癌(GC)进展过程中的确切作用和调节机制知之甚少。在本研究中,我们发现 UCA1 在胃癌组织中异常升高,与淋巴结转移和 TNM 分期显著相关。在体内和体外,强制升高 UCA1 水平促进 GC 细胞的迁移和侵袭。耗尽 UCA1 的表达水平可减弱 GC 细胞迁移和侵袭的能力。然后,我们检测到转录因子 ZEB2 的表达水平受 UCA1 在 GC 细胞中的调节。miR-203 靶向并抑制 ZEB2 的表达。此外,我们发现 UCA1 可以直接与 miR-203 相互作用,导致 miR-203 靶向转录本 ZEB2 的释放。在此,我们揭示了 UCA1 在 GC 转移过程中通过海绵调节轴调节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 GC 中发挥关键作用。探索 UCA1-miR-203-ZEB2 轴的功能可能为恶性肿瘤提供有价值的生物标志物和高度选择性的抗 GC 治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15d7/6249325/deadb125a9e0/41419_2018_1170_Fig1_HTML.jpg

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