Abstract A42: LncRNA-p23154--miR-375 axis regulates OSCC glycolysis by targeting SCL2A1
Authors: Yun Wang, Bin Cheng
Journal: Cancer Research (2016)

Abstract Objective: Accumulating data have shown that the deregulation of microRNA involved in the occurrence and development of human cancer. However, the expression profile and function of long non-coding RNA (lncRNA) in cancerous processes is still unclear, especially in oral squamous cell carcinoma (OSCC) glycolysis. In this study, we attempted to explore the function and mechanisms of lncRNA/microRNA in OSCC glycolysis, and hoped to provide a novel diagnostic and therapeutic strategy for OSCC patient. Methods: In order to identify a new lncRNA-microRNA axis that regulates the glycolysis in OSCC, we performed a microarray assay to explore the lncRNA/microRNA expression profiling in OSCC samples and adjacent non-tumor tissues (controls) from 4 patients. Quantitative RT (qRT)-PCR and functional analysis were used to confirm the role of lncRNA/microRNA, which we focused on, in OSCC glycolysis. Then we predicted the targeted gene of microRNA through a bioinformatics approach and defined it by luciferase assay and western blot. Luciferase assay and qRT-PCR were also used to verify the relation between lncRNA and microRNA. At last, we utilized the node mouse model to detect the effect of lncRNA/microRNA in OSCC glycolysis in vivo. Results: Here, we established the role and mechanisms of lncRNA-p23154-miR-375 axis in glycolysis of OSCC. First, we profiled lncRNA/microRNA expression in OSCC tissues and the paired normal tissues from four patients. LncRNA-p23154 was up-regulated in cancer tissues than in normal tissues, while miR-375 was down-regulated significantly. These observations were confirmed in 20 pairs of tissues and five cohorts of OSCC cell lines. Functional analysis showed that ectopic expression of miR-375 repressed the OSCC cell proliferation and glycolysis; on the other hand, miR-375 inhibition resulted in increased the proliferation and glycolysis. At the same time, the silencing of lncRNA-p23154 inhibited the OSCC cell proliferation and glycolysis, while overexpression of lncRNA-p23154 had the opposite effect. Consistently, the xenograft mouse model unveiled that the suppressive effects of miR-375 on OSCC tumor growth, as well as lncRNA-p23154 could accelerate the tumor growth. Furthermore, the expression level of SCL2A1, which encodes a major glucose transporter in the cell membrane, was repressed when overexpressing the miR-375 expression in OSCC cells, whereas miR-375 silencing increased its expression. Next, we showed that miR-375 could bind to the 3'-untranslated region of SCL2A1 by luciferase reporter assay. Moreover, we demonstrated that lncRNA-p23154 could regulate the OSCC proliferation and glycolysis by inhibiting the activation of miR-375 expression. Conclusion: Taken together, our findings indicated that the lncRNA-p23154–miR-375 axis acts as an important regulator in OSCC cell proliferation and glycolysis through inhibiting SCL2A1 expression. Manipulation of lncRNA-p23154/ miR-375 may provide a promising diagnostic and therapeutic strategy for oral cancer treatment. Citation Format: Yun Wang, Bin Cheng. LncRNA-p23154--miR-375 axis regulates OSCC glycolysis by targeting SCL2A1. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A42.