Circular RNA circ_0006523 promotes lipid accumulation and proliferation of diffuse large B-cell lymphoma via the miR-659-3p/SPHK1 axis

Abstract Dysregulated lipid metabolism is a core hallmark of diffuse large B-cell lymphoma (DLBCL), while the upstream non-coding RNA regulatory network targeting sphingosine kinase 1 (SPHK1), a key lipogenic kinase, remains largely uncharacterized in DLBCL. Here, we identified and validated a novel ceRNA regulatory axis consisting of circ_0006523, miR-659-3p, and SPHK1 in DLBCL clinical tissues and cell lines. circ_0006523 and SPHK1 were significantly upregulated, whereas miR-659-3p was downregulated, in DLBCL tissues and cell lines; high circ_0006523 expression was associated with advanced Ann Arbor stages (Ⅲ–IV). Mechanistically, RNase R-resistant circ_0006523 acted as a competing endogenous RNA (ceRNA) to sponge miR-659-3p, thus relieving its repression on SPHK1. Functionally, circ_0006523 promoted DLBCL cell proliferation and elevated intracellular lipid abundance via the miR-659-3p/SPHK1 axis. Collectively, the circ_0006523/miR-659-3p/SPHK1 axis modulates DLBCL proliferative phenotypes in vitro. Circ_0006523 expression correlates with advanced Ann Arbor stage in a limited DLBCL cohort, and this axis may provide preliminary molecular insights for further investigation in DLBCL.