PO-364 LncRNA-P23154 promotes the invasion-metastasis potential of oral squamous cell carcinoma by regulating Glut1-mediated glycolysis

Abstract

IntroductionThe dysregulation of glycolysis has been suggested to lead to the alteration of cell drug resistancesignals, proliferation and metastasis. Emerging evidence indicates that lncRNAs play a key role inthe cellular processes of tumour cells, including glycolysis, growth, and movement. However, therole of lncRNAs in glycolysis-mediated metastasis and the potential mechanism has not been explored.Material and methodsFirst, microarrays were performed to explore the lncRNA, mRNA and miRNA profiles in 4 pair OSCC and adjacent non-tumour tissue samples. qRT-PCR and bioinformatic analysis were used to confirm the expression and coding capability of lnc-p23154 in OSCC cell lines. Then, functional experiment, the nude mouse model and RNA sequence were performed to demonstrated that lnc-p23154 could promote OSCC metastasis and glycolysis both in vitro and in vivo. Furthermore, we verified lnc-p23154 promoted OSCC metastasis via Glut1-mediated glycolysis through a rescue assay. At last, luciferase assay, FISH assay, RNA immunoprecipitation and RNA pull down was utilised to prove that lnc-p23154 inhibited miR-378a-3p transcription by interacting with its promoter region, then regulated miR-378a-3p targeted gene Glut1 expression and promoted Glut1-mediated OSCC metastasis.Results and discussionsIn this study, we identified a novel lncRNA, lnc-p23154, which is up-regulated in oralsquamous cell carcinoma (OSCC) tissues and cell lines, is associated with OSCC patientmetastasis and promotion of OSCC cell migration and invasion in vitro and in vivo. Furthermore,we found that lnc-p23154 also participates in OSCC glycolysis by facilitating Glut1 expression.Rescue of lnc-p23154 reversed the suppression of OSCC cell migration and invasion induced byGlut1 knockdown. More importantly, lnc-p23154 is mainly located in the nucleus and binds to thepromoter region of miR-378a-3p, which represses Glut1 expression by targeting to its 3'UTRdirectly.ConclusionIn summary, we described a novel mechanism of lnc-p23154-miR-378a-3p/Glut1 axis inGlut1-mediated glycolysis and OSCC metastasis regulation. Meanwhile, we provided evidencethat overexpression of lnc-p23154 is significantly associated with higher metastasis tendency inboth OSCC cells and patients with OSCC. These results indicated that lnc-p23154 may act as ametastasis driver in OSCC and a potential biomarker for OSCC diagnosis and treatment.