AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma

• Published in: Oncogene Vol. 39; no. 34; pp. 5616 - 5632
• Main Authors: He, Shi-Wei, Xu, Cheng, Li, Ying-Qing, Li, Ying-Qin, Zhao, Yin, Zhang, Pan-Pan, Lei, Yuan, Liang, Ye-Lin, Li, Jun-Yan, Li, Qian, Chen, Yang, Huang, Sheng-Yan, Ma, Jun, Liu, Na
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20-08-2020; Nature Publishing Group
• Subjects: 631/67/1536; 631/80/84; 692/53/2422; Androgen receptors; Animals; Apoptosis; Cancer; Carcinoma; Cell Biology; Cell growth; Cell Line; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Development and progression; Ectopic expression; Gene Expression Regulation, Neoplastic; Glutamine; HEK293 Cells; Human Genetics; Humans; Internal Medicine; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Carcinoma - therapy; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - therapy; Non-coding RNA; Oncology; Prognosis; Proline; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; PTB-Associated Splicing Factor - genetics; PTB-Associated Splicing Factor - metabolism; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; RNA; RNA Interference; RNA, Long Noncoding - genetics; Splicing factors; Throat cancer; Transcription activation; Tumorigenesis; Xenograft Model Antitumor Assays - methods
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-020-01388-8

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.