LINC01376 promotes nasopharyngeal carcinoma tumorigenesis by competitively binding to the SP1/miR‐4757/IGF1 axis

Abstract

AbstractThe long non‐coding RNA (lncRNA)–microRNA (miRNA) interaction network plays a crucial part in the pathogenesis of nasopharyngeal carcinoma (NPC). Here, we discovered a relationship between LINC01376 and miR‐4757 in NPC tumor development. First, LINC01376 was abnormally overexpressed in NPC tissues and cells, and its elevated expression was associated with advanced clinical stage and shorter distant metastasis‐free survival time. Moreover, biological experiments showed that LINC01376 facilitated the proliferative, invasive, and migratory abilities of NPC cells in vitro and in vivo. Mechanistically, bioinformatics and RT‐qPCR assays revealed that LINC01376 knockdown upregulated the expression level of downstream miR‐4757, including miR‐4757 primary transcript (pri‐miR‐4757) and mature miR‐4757. Furthermore, LINC01376 competitively sponged the transcription factor SP1 and reduced its enrichment in the upstream promoter region of miR‐4757 to repress miR‐4757 expression. Finally, insulin‐like growth factor 1(IGF1) was identified as the target of miR‐4757. Rescue experiments indicated that LINC01376 accelerated NPC cell proliferation, migration, and invasion through the miR‐4757‐5p/IGF1 axis. In conclusion, the SP1/miR‐4757/IGF1 axis, which is regulated by LINC01376 in NPC deterioration and metastasis, is expected to provide new insights into the molecular mechanism of NPC carcinogenesis.