LINC02582 Sequesters MiR-375 to Facilitate Lung Metastasis in Colorectal Cancer Through Lactate Dehydrogenase B-Mediated Glycolysis

Abstract

Glycolysis plays a pivotal role in reprogramming the metastatic tumor microenvironment. Numerous long non-coding RNAs (lncRNAs) have been identified as oncogenic, orchestrating glycolytic pathways. In our study, we observed a progressive increase in LINC02582 expression from normal adjacent tissues to colorectal cancer (CRC) specimens, with a marked elevation in Stage IV tumors. Importantly, elevated levels of LINC02582 were associated with diminished survival rates, particularly in patients with pulmonary metastases. Functionally, LINC02582 was found to enhance glycolysis and the invasive potential of CRC cells in vitro, as well as augment their propensity for lung metastasis in vivo. Mechanistically, LINC02582 acts as a competitive endogenous RNA (ceRNA), modulating the expression of lactate dehydrogenase B (LDHB) through sequestration of miR-375. This interaction precipitates increased glycolytic activity in CRC cells, facilitating their invasion and subsequent metastasis to the lungs. Clinically, the concomitant overexpression of LINC02582 and LDHB serves as a prognostic indicator of poor survival outcomes in CRC patients. In summary, our findings designate LINC02582 as an oncogenic lncRNA in CRC, proposing the LINC02582/miR-375/LDHB axis as a novel prognostic biomarker for CRC patients with lung metastasis.