LINC01376 promotes nasopharyngeal carcinoma tumorigenesis by competitively binding to the SP1/miR-4757/IGF1 axis
LINC01376 promotes nasopharyngeal carcinoma tumorigenesis by competitively binding to the SP1/miR-4757/IGF1 axis
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DOI：
10.1002/iub.2721
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发表时间：
2023-03-27
期刊：
影响因子：
4.6
通讯作者：
He，Xia
中科院分区：
文献类型：
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作者：
Peng，Yi;Zhang，Yujie;He，Xia
长链非编码RNA（lncRNA）-microRNA（miRNA）相互作用网络在鼻咽癌（NPC）的发病机制中发挥着至关重要的作用。在这里，我们发现了LINC 01376和miR-4757在NPC肿瘤发展中的关系。首先，LINC 01376在NPC组织和细胞中异常过表达，其表达升高与晚期临床分期和较短的无远处转移生存期相关。此外，生物学实验表明，LINC 01376在体外和体内促进NPC细胞的增殖、侵袭和迁移能力。生物信息学和RT-qPCR分析显示，LINC 01376敲低上调了下游miR-4757的表达水平，包括miR-4757初级转录物（pri-miR-4757）和成熟miR-4757。此外，LINC 01376竞争性地吸收转录因子SP1并减少其在miR-4757上游启动子区的富集，从而抑制miR-4757表达。最后，胰岛素样生长因子1（IGF 1）被确定为miR-4757的靶点。拯救实验表明，LINC 01376通过miR-4757 - 5 p/IGF 1轴加速NPC细胞增殖、迁移和侵袭。综上所述，LINC 01376调控的SP1/miR-4757/IGF 1轴在NPC恶化和转移中的作用有望为NPC癌变的分子机制提供新的见解。
The long non‐coding RNA (lncRNA)–microRNA (miRNA) interaction network plays a crucial part in the pathogenesis of nasopharyngeal carcinoma (NPC). Here, we discovered a relationship between LINC01376 and miR‐4757 in NPC tumor development. First, LINC01376 was abnormally overexpressed in NPC tissues and cells, and its elevated expression was associated with advanced clinical stage and shorter distant metastasis‐free survival time. Moreover, biological experiments showed that LINC01376 facilitated the proliferative, invasive, and migratory abilities of NPC cells in vitro and in vivo. Mechanistically, bioinformatics and RT‐qPCR assays revealed that LINC01376 knockdown upregulated the expression level of downstream miR‐4757, including miR‐4757 primary transcript (pri‐miR‐4757) and mature miR‐4757. Furthermore, LINC01376 competitively sponged the transcription factor SP1 and reduced its enrichment in the upstream promoter region of miR‐4757 to repress miR‐4757 expression. Finally, insulin‐like growth factor 1(IGF1) was identified as the target of miR‐4757. Rescue experiments indicated that LINC01376 accelerated NPC cell proliferation, migration, and invasion through the miR‐4757‐5p/IGF1 axis. In conclusion, the SP1/miR‐4757/IGF1 axis, which is regulated by LINC01376 in NPC deterioration and metastasis, is expected to provide new insights into the molecular mechanism of NPC carcinogenesis.