lncRNA FOXP4-AS1 predicts poor prognosis and accelerates the progression of mantle cell lymphoma through the miR-423-5p/NACC1 pathway

Long non-coding RNA (lncRNA) forkhead box P4 antisense RNA 1 (FOXP4-AS1) has been determined to function as an oncogene in various types of cancer. However, the biological function and the underlying mechanisms of FOXP4-AS1 in mantle cell lymphoma (MCL) remain to be uncovered. The expression and the associated clinicopathological characteristics and prognostic significance of FOXP4-AS1 were explored in MCL clinical samples. The effects of FOXP4-AS1 on MCL cellular behaviors, including proliferation, migration and invasion were analyzed using CCK-8, crystal violet and Transwell assays. The downstream molecules of FOXP4-AS1 were explored using bioinformatics analysis and dual luciferase assay. Our results showed that FOXP4-AS1 expression was upregulated in MCL patients, and that the high expression of FOXP4-AS1 was correlated with the unfavorable prognosis of patients. Functionally, while FOXP4-AS1 downregulation inhibited proliferation, migration and invasion of MCL cells, FOXP4-AS1 overexpression had promotive effects on these cellular processes. Mechanistically, FOXP4-AS1 was found to act as a competing endogenous (ce)RNA for miR-423-5p to regulate the expression of nucleus accumbens-associated 1 (NACC1). The negative regulation of FOXP4-AS1 on miR-423-5p compared to that of miR-423-5p on NACC1 was determined at the mRNA or protein levels in MCL cells. Moreover, an inverse expression correlation between FOXP4-AS1 and miR-423-5p, and that between miR-423-5p and NACC1 was confirmed in MCL clinical samples. In addition, rescue assay showed that miR-423-5p upregulation or NACC1 knockdown abolished the promoting effects of FOXP4-AS1 on MCL cell proliferation, migration and invasion. In conclusion, FOXP4-AS1 promotes MCL progression through the upregulation of NACC1 expression by inhibiting miR-423-5p. FOXP4-AS1 may serve as a novel therapeutic target for patients with MCL.