SP1-Mediated Upregulation of lncRNA LINC01614 Functions a ceRNA for miR-383 to Facilitate Glioma Progression Through Regulation of ADAM12

Background: Long non-coding RNAs (lncRNAs) play an imperative role in tumorigenesis, but few lncRNAs have been functionally characterized in glioma. The aim of the present study was to identify the role of long non-coding RNA LINC01614 (LINC01614) in glioma development and explore the underlying mechanisms of LINC01614/miR-383/ADAM12 axis.

Patients and methods: LncRNA expression in glioma specimens was measured by lncRNA microarray and qRT-PCR. The prognostic value of LINC01614 expression was statistically analyzed in 112 glioma patients. Loss-of-function experiments were conducted to investigate the biological functions of LINC01614 in vitro. Luciferase analyses, ChIP assays, and RNA pull-down were performed to determine the underlying LINC01614 mechanisms.

Results: We identified a novel glioma-related lncRNA LINC01614 by analyzing TCGA datasets. The distinct upregulation of LINC01614 was observed in both glioma specimens and cell lines using RT-PCR. We also observed that LINC01614 upregulation was induced by nuclear transcription factor SP1. Clinical assays revealed that high levels of LINC01614 were associated with KPS, WHO grade and shorter overall survival of glioma patients. Multivariate analysis further confirmed that LINC01614 was an independent prognostic marker for glioma patients. Besides, functional assays displayed that silence of LINC01614 knockdown distinctly inhibited cell growth, migration and invasion and promoted cell Apoptosis in glioma cells. LINC01614 expression was enriched in the cytoplasm of glioma cells. Mechanistic investigation revealed that LINC01614 functioned as a competing endogenous RNA to upregulate a disintegrin and metalloproteinase 12 (ADAM12) by sponging miR-383.

Conclusion: Overall, these findings showed that SP1-induced upregulation of LINC01614 promoted glioma malignant progression via modulating the miR-383/ADAM12 axis, which may provide a promising therapy for glioma.