Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia.
Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia.
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长链非编码RNA BC005927上调EPHB4并促进缺氧下胃癌转移
DOI：
10.1111/cas.13519
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发表时间：
2018-04
期刊：
影响因子：
5.7
通讯作者：
Liu L
中科院分区：
文献类型：
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作者：
Liu X;Wang Y;Sun L;Min J;Liu J;Chen D;Zhang H;Zhang H;Zhang H;Zhou Y;Liu L
缺氧在胃癌的转移中起着重要作用，但其机制尚不清楚。长链非编码RNA（lncRNA）是否参与缺氧对胃癌转移的作用也不清楚。在本研究中，我们发现lncRNA BC 005927可以在GC细胞中由缺氧诱导并介导缺氧诱导的GC细胞转移。此外，BC 005927在GC样品中频繁上调，并且BC 005927表达增加与较高的肿瘤淋巴结转移阶段相关。BC 005927高表达的胃癌患者比低表达的胃癌患者预后差。其他实验表明，BC 005927的表达是由缺氧诱导因子-1 α（HIF-1α）诱导的; ChIP试验和荧光素酶报告基因试验证实，该lncRNA是HIF-1α的直接转录靶点。接下来，我们发现转移相关基因EPHB 4受BC 005927调控，并且EPHB 4的表达与评估的临床GC样品中的BC 005927的表达呈正相关。有趣的是，EPHB 4表达在缺氧下也增加，并且其被BC 005927上调导致缺氧诱导的GC细胞转移。这些结果推进了目前对BC 005927在缺氧信号调节中的作用的理解，并为开发针对癌症进展的治疗干预提供了新的途径。
Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known whether long, noncoding RNAs (lncRNAs) are involved in the contribution of hypoxia to GC metastasis. In the present study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia‐induced GC cell metastasis. Furthermore, BC005927 is frequently upregulated in GC samples and increased BC005927 expression was correlated with a higher tumor‐node‐metastasis stage. GC patients with higher BC005927 expression had poorer prognoses than those with lower expression. Additional experiments showed that BC005927 expression is induced by hypoxia inducible factor‐1 alpha (HIF‐1α); ChIP assay and luciferase reporter assays confirmed that this lncRNA is a direct transcriptional target of HIF‐1α. Next, we found that EPHB4, a metastasis‐related gene, is regulated by BC005927 and that the expression of EPHB4 was positively correlated with that of BC005927 in the clinical GC samples assessed. Intriguingly, EPHB4 expression was also increased under hypoxia, and its upregulation by BC005927 resulted in hypoxia‐induced GC cell metastasis. These results advance the current understanding of the role of BC005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
通讯作者：
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受体酪氨酸激酶EPHB4在卵巢癌中过表达，提供生存信号并预测结果不佳。
影响因子：
8.8
作者：
Kumar, S. R.;Masood, R.;Spannuth, W. A.;Singh, J.;Scehnet, J.;Kleiber, G.;Jennings, N.;Deavers, M.;Krasnoperov, V.;Dubeau, L.;Weaver, F. A.;Sood, A. K.;Gill, P. S.
通讯作者：
Gill, P. S.
影响因子：
5.4
作者：
Kornienko AE;Guenzl PM;Barlow DP;Pauler FM
通讯作者：
Pauler FM
影响因子：
4.5
作者：
Kapusta A;Kronenberg Z;Lynch VJ;Zhuo X;Ramsay L;Bourque G;Yandell M;Feschotte C
通讯作者：
Feschotte C