LBX2-AS1 in acceleration of glycolysis and cancer angiogenesis via miR-491-5p/MDK signaling axis in colorectal cancer: an experimental study

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. 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 <i>in vitro</i>. 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 <i>in vivo</i>. As a marker of poor prognosis, LBX2-AS1 was highly expressed in CRC tumor tissues and cells (all <i>p</i> &lt; 0.01). Downregulation of LBX2-AS1 inhibited the proliferation, migration, and invasion of CRC cells (all <i>p</i> &lt; 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 <i>p</i> &lt; 0.01). Overexpression of MDK reversed the downregulation of LBX2-AS1 inhibition of these biological activities in CRC cells (all <i>p</i> &lt; 0.01). Downregulation of LBX-AS1 inhibited tumor growth and angiogenesis <i>in vivo</i> (all <i>p</i> &lt; 0.001). Overexpression of MDK reversed the downregulation of LBX2-AS1 inhibition of tumor growth and angiogenesis <i>in vivo</i> (all <i>p</i> &lt; 0.001). Mechanistically, LBX2-AS1 regulated MDK transcription by mediating miR-491-5p. This study demonstrates that LBX2-AS1 promotes CRC angiogenesis and activates the glycolysis <i>via</i> the miR-491-5p/MDK axis. LBX2-AS may serve as a novel diagnostic biomarker and potential therapeutic target for CRC.