Abstract 2545: Upregulated lncRNA-HNGA1, a target of miR-378a, contributes to aerobic glycolysis of head and neck squamous cell carcinoma through increasing levels of the C-C chemokine receptor type 7 (CCR7)

Abstract

Abstract Introduction: Long non-coding RNAs (lncRNAs) have been regarded as key regulators in aerobic glycolysis of human cancer. However, the role and function of lncRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) aerobic glycolysis remain unclear. Here, we report a novel lncRNA, HNGA1, which could promote HNSCC aerobic glycolysis and malignancy by competing for miR-378a binding to regulate CCR7. Materials and methods: Microarrays were performed to explore the lncRNA/miRNA profiles in tissues samples. qRT-PCR and functional analysis were used to confirm the expression and role of lncRNA/miRNA. Bioinformatics approach and luciferase assay were used to verify the miRNA target gene and the interation between lncRNA and miRNA. Nude mouse model was utilized to observe the effect of lncRNA/miRNA in vivo. Tissue array was performed to explore the association between lncRNA and postoperative survival. Results: 1. LncRNA HNSCC glycolysis-associated 1 (HNGA1) was up-regulated in tumor tissues, while miR-378a was down-regulated significantly. These observations were confirmed in 60 pairs of HNSCC tissues/non-tumor tissues samples and 7 cohorts of HNSCC cell lines. 2. Silencing of HNGA1 inhibited HNSCC cells proliferation and glycolysis, while overexpression of HNGA1 had the opposite effect. 3. Ectopic expression of miR-378a repressed HNSCC cells proliferation and glycolysis, whereas miR-378a inhibition resulted in the opposite effect. MiR-378a could repress the CCR7 expression by binding to the 3’-UTR region of CCR7 directly. 4. There was an inverse correlation between HNGA1 and miR-378a in HNSCC specimens. Moreover, miR-378a suppressed HNGA1’s expression and function by directly binding to HNGA1. In addition, HNGA1 could reverse the inhibitory effect of miR-378a on HNSCC cells, which might act as an endogenous ‘sponge’ by competing for miR-378a binding to regulate CCR7. 5. The xenograft mouse model unveiled the suppressive effects of miR-378a on HNSCC tumor growth and glycolysis, while HNGA1 could accelerate this process. 6. The clinicopathological findings suggested that the up-regulation of HNGA1 in HNSCC patients was associated with the poorly differentiated degree and more metastasis. Moreover, the results of tissue array showed that HNGA1 was correlated with postoperative survival. Conclusion: Taken together, our data highlights the pivotal role of HNGA1 in HNSCC aerobic glycolysis. More importantly, we elucidate a novel lncRNA-miRNA-mRNA regulatory network that is HNGA1-miR-378a-CCR7 axis in HNSCC malignancy and progression. Citation Format: Yun Wang. Upregulated lncRNA-HNGA1, a target of miR-378a, contributes to aerobic glycolysis of head and neck squamous cell carcinoma through increasing levels of the C-C chemokine receptor type 7 (CCR7) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2545. doi:10.1158/1538-7445.AM2017-2545