Abstract
BACKGROUND: Recent studies have identified various roles for long non-coding RNAs (lncRNAs) in cancer progression. However, an in-depth understanding of the regulatory mechanisms of lncRNAs in colorectal cancer (CRC) and their diagnostic significance is rather limited. MATERIALS AND METHODS: The diagnostic value of LBX2 antisense RNA 1 (LBX2-AS1) was assessed using public databases and clinical samples. Cell-counting kit 8 (CCK-8), Colony Formation, transwell, and wound scratch assays were performed to assess CRC cell proliferation and metastasis in vitro. Glucose consumption, lactate production, adenosine triphosphate (ATP), extracellular acidification rate (ECAR), and oxygen composition rate (OCR) were evaluated in CRC cells. A dual luciferase assay was used to verify the target-binding relationship of LBX2-AS1/microRNA (miR)-491-5p/midkine (MDK). BALB/C nude mice were used to establish a subcutaneous xenograft mouse model. The role of the LBX2-AS1/MDK axis in CRC proliferation and angiogenesis was analyzed in vivo. RESULTS: As a marker of poor prognosis, LBX2-AS1 was highly expressed in CRC tumor tissues and cells (all p < 0.01). Downregulation of LBX2-AS1 inhibited the proliferation, migration, and invasion of CRC cells (all p < 0.01). Furthermore, the levels of glucose consumption, lactate production, ATP, ECAR, glycolytic-related indicators, and markers of angiogenesis were also inhibited by the downregulation of LBX2-AS2 expression (all p < 0.01). Overexpression of MDK reversed the downregulation of LBX2-AS1 inhibition of these biological activities in CRC cells (all p < 0.01). Downregulation of LBX-AS1 inhibited tumor growth and angiogenesis in vivo (all p < 0.001). Overexpression of MDK reversed the downregulation of LBX2-AS1 inhibition of tumor growth and angiogenesis in vivo (all p < 0.001). Mechanistically, LBX2-AS1 regulated MDK transcription by mediating miR-491-5p. CONCLUSION: This study demonstrates that LBX2-AS1 promotes CRC angiogenesis and activates the glycolysis via the miR-491-5p/MDK axis. LBX2-AS may serve as a novel diagnostic biomarker and potential therapeutic target for CRC.