LINC00491 promotes nasopharyngeal carcinoma metastasis by binding to purine-rich element binding protein alpha and regulating annexin-A1 to activate the PI3K/AKT pathway.

BACKGROUND

Distant metastasis and locoregional recurrence represent the predominant causes of therapeutic inefficacy in nasopharyngeal carcinoma (NPC), highlighting an urgent need for discovery of novel molecular targets. Current evidence suggests that LINC00491 is involved in the tumorigenesis and progression of pulmonary adenocarcinoma, pancreatic carcinoma, and other malignancies. Nevertheless, its functional role and precise molecular mechanisms in NPC remain to be fully elucidated.

METHODS

Gene screening was performed through lncRNA sequencing. LINC00491 expression in NPC specimens was detected via in situ hybridization (ISH), and its correlation with clinicopathological features and patient prognosis was evaluated. Functional roles of LINC00491 were investigated through in vitro assays (Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine，wound healing, and Transwell) and in vivo experiments (tumor xenograft and lung metastasis in nude mice). Mechanistically, the subcellular localization of LINC00491 was detected by fluorescence in situ hybridization (FISH). The expression of genes and proteins was examined by reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot (WB) to investigate its regulatory effects. Proteins directly bound by LINC00491 were identified by RNA pull-down combined with mass spectrometry (MS) and by RNA immunoprecipitation (RIP).

RESULTS

LINC00491 was identified through LncRNA sequencing screening and showed pronounced upregulation in NPC tissues and cells. High LINC00491 expression was linked to significantly shorter survival times. Functional assays demonstrated that LINC00491 significantly enhances neoplastic proliferation and distant metastasis both in vitro and in vivo, suggesting a strong link between its overexpression and poor clinical outcomes. Mechanistically, LINC00491 directly binds to purine-rich element binding protein alpha (PURα), and its upregulation induces the translocation of PURα from the nucleus to the cytoplasm, which likely attenuates the transcriptional repressive activity of PURα on annexin-A1 (ANXA1), thereby promoting ANXA1 expression. Furthermore, LINC00491 drives aberrant activation of the PI3K/AKT pathway via ANXA1, leading to alterations in epithelial-mesenchymal transition (EMT)-related protein expression and ultimately facilitating nasopharyngeal carcinoma metastasis.

CONCLUSIONS

LINC00491 promotes NPC metastasis by interacting with PURα to regulate ANXA1 expression and activate the PI3K/AKT signaling pathway. The results demonstrate that LINC00491-PURα-ANXA1 axis as a promising therapeutic target for NPC.