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

Oncogene. 2020 Aug;39(34):5616-5632. doi: 10.1038/s41388-020-01388-8. Epub 2020 Jul 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / therapy
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / therapy
  • PTB-Associated Splicing Factor / genetics*
  • PTB-Associated Splicing Factor / metabolism
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • AR protein, human
  • PTB-Associated Splicing Factor
  • Proto-Oncogene Proteins c-fos
  • RNA, Long Noncoding
  • Receptors, Androgen
  • fos-related antigen 1