lncRNA NEAT1 promotes the proliferation of hemangioma cells by transcriptionally activating β‑catenin via enhancing H3K18 lactylation

Infantile hemangioma (IH), a common vascular tumor, occurs in childhood; however, its pathogenesis has not been fully elucidated. In the present study, the roles and detailed mechanisms of long non‑coding RNA (lncRNA) NEAT1 in the progression of hemangioma were further explored. The NEAT1‑interacting proteins were selected by analyzing the catRAPID database and Lactate Dehydrogenase B (LDHB) was predicted to bind with NEAT1. The binding between NEAT1 and LDHB was validated using an RNA immunoprecipitation assay and it was further found that knocking down NEAT1 expression destabilized LDHB by regulating the Proteasome pathway. The knocking down of lncRNA NEAT1 also inhibited cellular protein lactylation and downregulated β‑catenin. Furthermore, blockade of lactylation via 2‑DG and oxamate attenuated the viability and colony formation of hemangioma cells. NEAT1 promoted the lactylation of H3K18 in the promoter region of β‑catenin, and blockade of lactylation downregulated β‑catenin expression in hemangioma cells. The lactyltransferases alanyl‑tRNA synthetase 1 and P300 were regulated by NEAT1 and also positively regulated β‑catenin. The levels of β‑catenin mRNA and H3K18 lactylation were also found to be elevated in IH tissues. Taken together, the results of the present study revealed that lncRNA NEAT1, which is upregulated in hemangioma, binds with and stabilizes LDHB, subsequently elevates the levels of cellular lactate and H3K18 lactylation, potentiates β‑catenin transcription and ultimately enhances the proliferation of hemangioma cells.

H3K18; NEAT1; lactate dehydrogenase B; lactylation; β‑catenin.