AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma
AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma
复制标题
AR诱导的长非编码RNA LINC01503通过SFPQ-FOSL1轴促进鼻咽癌的增殖和转移
DOI：
10.1038/s41388-020-01388-8
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发表时间：
2020-07-13
期刊：
影响因子：
8
通讯作者：
Liu, Na
中科院分区：
文献类型：
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作者：
He, Shi-Wei;Xu, Cheng;Liu, Na
越来越多的证据表明，长的非编码RNA(LncRNAs)在肿瘤的发生和发展中起着重要的作用。然而，LncRNAs在鼻咽癌中的功能和调控机制目前仍不清楚。我们先前的LncRNA表达谱表明LINC01503在鼻咽癌中高表达。在此，我们证实LINC01503在鼻咽癌中高表达，并与预后不良相关。LINC01503在体外促进鼻咽癌细胞的增殖、迁移和侵袭，在体内促进肿瘤的生长和转移。在机制上，LINC01503招募富含脯氨酸和谷氨酰胺的剪接因子(SFPQ)激活Fos like 1(FOSL1)转录，FOSL1的异位表达逆转了LINC01503基因敲除对鼻咽癌进展的抑制作用。此外，雄激素受体(AR)介导的转录激活是导致LINC01503过表达以及AR配体依赖的鼻咽癌细胞生长、迁移和侵袭的原因。综上所述，我们的研究结果表明，AR诱导的LINC01503可以通过SFPQ-FOSL1轴促进鼻咽癌的进展，这可能是一种新的鼻咽癌预后生物标志物和治疗靶点。
Increasing evidence indicates that long non-coding RNAs (lncRNAs) play vital roles in the tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in nasopharyngeal carcinoma (NPC) are still largely unknown. Our previous lncRNA expression profiles identified that LINC01503 was overexpressed in NPC. Here, we verified that LINC01503 was highly expressed in NPC and correlated with poor prognosis. LINC01503 promoted NPC cell proliferation, migration, and invasion in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, LINC01503 recruited splicing factor proline-and glutamine-rich (SFPQ) to activate Fos like 1 (FOSL1) transcription, and ectopic expression of FOSL1 reversed the suppressive effect of LINC01503 knockdown on NPC progression. Moreover, androgen receptor (AR)-mediated transcription activation was responsible for the overexpression of LINC01503, and AR ligand-dependent cell growth, migration, and invasion in NPC cells. Taken together, our findings reveal that AR-induced LINC01503 can promote NPC progression through the SFPQ-FOSL1 axis, which represents a novel prognostic biomarker and therapeutic target for NPC patients.