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

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.

Identification of Epithelial-Mesenchymal Transition-Related lncRNAs that Associated With the Prognosis and Immune Microenvironment in Colorectal Cancer

“…And the results proved that our findings are accurate and reliable. For example, LINC01503 was confirmed to be correlated with the OS of CRC patients, and other studies have also found that it is highly expressed in different tumor cells, and is positively correlated with tumor cell proliferation and metastasis, including nasopharyngeal carcinoma ( He et al, 2020 ), gastric cancer ( Ding et al, 2020 ; Ma et al, 2020 ), and CRC ( Wei et al, 2020 ). Interestingly, in cholangiocarcinoma, LINC01503 can also promote the EMT process ( Qu et al, 2019 ), confirming that this lncRNA is an EMT-related lncRNA.…”

GATA1-induced upregulation of LINC01503 promotes carboplatin resistance in ovarian carcinoma by upregulating PD-L1 via sponging miR-766-5p

“…As demonstrated by accumulated evidence, LINC01503 aggravates the progression of several malignancies, such as nasopharyngeal carcinoma [ 31 ], cholangiocarcinoma [ 32 ], and hepatocellular carcinoma [ 33 ]. According to an investigation performed with TCGA, LINC01503 was highly expressed in OV tissues, compared with corresponding normal tissues.…”

Metastasis of nasopharyngeal carcinoma: What we know and do not know

“…Long non-coding RNA FAM225A acts as ceRNA to sponge miR-590-3p/miR-1275 and upregulates ITGB3 to promote NPC metastasis [114]. Long non-coding RNA LINC01503 stimulates NPC metastasis by recruiting splicing factor proline-and glutamine-rich (SFPQ) to activate Fos-like 1 (FOSL1) transcription [115]. MicroRNA-494-3p promotes NPC cellular motility and growth by targeting Sox7 [116].…”