小细胞肺癌（SCLC）是一种具有极差预后的最恶性的肿瘤之一。RNA结合蛋白（RBP）和长链非编码RNA（lncRNA）已被证明在肿瘤发生以及肺肿瘤进展过程中是关键调控因子。然而，RBP ELAVL4和lncRNA LYPLAL1-DT在SCLC中的作用仍不清楚。本研究验证了lncRNA LYPLAL1-DT作为一种SCLC的致癌性lncRNA，并在体外和体内得到了确认。在机制上，LYPLAL1-DT通过负调节miR-204-5p的表达，从而导致PFN2的上调，进而促进SCLC细胞的增殖、迁移和侵袭。ELAVL4已被证明增强LYPLAL1-DT和PFN2 mRNA的稳定性。我们的研究揭示了一个调节途径，其中ELAVL4通过稳定PFN2和LYPLAL1-DT，而LYPLAL1-DT通过阻断miR-204-5p的作用进一步增加PFN2的表达。上调的PFN2最终促进了SCLC的肿瘤发生和侵袭。这些发现为SCLC提供了新的预后指标和有希望的治疗靶点。©2023年美国实验生物学联合会。

Small cell lung cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.© 2023 Federation of American Societies for Experimental Biology.