Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR-30a-3p in non-small cell lung cancer
Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR-30a-3p in non-small cell lung cancer
复制标题
缺氧敏感的 LINC01436 受 E2F6 调节，通过靶向肺腺癌中的 miR-30a-3p 作为癌基因。
DOI：
10.1002/1878-0261.12437
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发表时间：
2019-04-01
影响因子：
6.6
通讯作者：
Li, Yafei
中科院分区：
文献类型：
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作者：
Yuan, Shuai;Xiang, Ying;Li, Yafei
已知长链非编码RNA（lncRNA）的失调与包括肺癌在内的许多人类疾病有关。然而，大多数lncRNA的确切生物学功能仍有待阐明。在这里，我们在非小细胞肺癌（NSCLC）中鉴定了一种新的上调lncRNA，LINC 01436（RefSeq：NR_110419.1）。LINC 01436的高表达与总生存率显著相关。值得注意的是，LINC 01436表达在常氧下被E2 F6转录抑制，并且在缺氧微环境中抑制作用被缓解。功能获得和丧失研究表明，LINC 01436作为原癌基因通过促进肺癌细胞的生长、迁移和体外侵袭而发挥作用。裸鼠中的异种移植肿瘤测定证实LINC 01436促进体内肿瘤生长和转移。LINC 01436通过作为microRNA（miR）-30a-3p海绵来调节其靶基因EPAS 1的表达而发挥生物学功能。我们的研究结果将LINC 01436描述为一种新的缺氧敏感性lncRNA，在NSCLC中具有致癌功能，这表明LINC 01436可能是预后的潜在生物标志物和治疗的潜在靶点。
Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up-regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non-small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain- and loss-of-function studies revealed that LINC01436 acted as a proto-oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)-30a-3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia-sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.