Identification and validation of a novel LncRNA TRG-AS1 that inhibits colorectal cancer proliferation and glycolysis

Background: Glucose metabolism reprogramming is one of the major hallmarks of malignant tumors and is regulated by long non-coding RNA (LncRNA). However, the role of glycolysis-associated LncRNA in colorectal cancer (CRC) remains largely unknown. In this study, we identified a novel LncRNA TRG-AS1 that inhibits CRC glycolysis and proliferation through comprehensive bioinformatics analysis and experimental validation. Methods TRG-AS1 overexpressing stable cell line and silence the target gene cell line were generated. Glucose assay kits and Pyruvate assay kits were utilized to analyze glycolysis. The cell proliferation ability was evaluated by CCK8, Colony formation assays and EdU. Xenograft tumor experiments were performed to assess proliferative capacity. Cell migration and invasion abilities were examined using the Transwell assay. Results TRG-AS1 was significantly down-regulated in CRC tumors as revealed by nine independent CRC cohorts, including our own in-house cohort. Clinically, high expression of TRG-AS1 predicts favorable overall survival (OS) and disease-free survival (DFS) in CRC patients, and high level of TRG-AS1 is closely associated with earlier tumor stage. In terms of function, over-expression of TRG-AS1 significantly inhibited CRC aerobic glycolysis, proliferation, metastasis potential and tumor growth, while knockdown of TGR-AS1 dramatically promoted CRC aerobic glycolysis and progression. Data based on bioinformatics analysis suggest that TRG-AS1 may be involved in CRC progression by influencing glycolysis-related molecules, such as SLC2A1, PGK1 and ENO1, etc. Conclusion Our study advances the understanding that LncRNA inhibits CRC glycolysis and progression, and provide a promising molecular target for the treatment of CRC.