LINC02126 stabilized by YTHDC1-mediated m6A modification suppresses lung adenocarcinoma progression by sponging...

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer, characterized by high incidence and mortality rates. Long noncoding RNAs (lncRNAs) have gained increasing attention for their regulatory roles in tumors, but the functions of many lncRNAs remain poorly understood. Previous studies have suggested that LINC02126 is downregulated in LUAD, yet its specific biological function remains unclear. This study aimed to investigate the role of LINC02126 in LUAD and to elucidate the underlying molecular mechanisms.

RT-qPCR and Western blotting were employed to detect mRNA and protein expression levels. Cell viability, proliferation, cell cycle distribution, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, EdU, flow cytometry, wound healing, and transwell assays. MeRIP-qPCR, m6A-IP-qPCR, RNA pull-down, dual-luciferase reporter, and RNA stability assays were used to evaluate LINC02126 m6A modification and its interaction with YTHDC1. The target miRNA was identified via bioinformatics combined with dual-luciferase reporter, Ago2-RIP, and RNA pull-down assays. A nude mouse xenograft model was used to examine tumor growth in vivo.

LINC02126 was significantly downregulated in LUAD and associated with poor prognosis. Overexpression of LINC02126 inhibited proliferation, migration, invasion, and EMT, while promoting apoptosis and cell cycle arrest. YTHDC1 bound to LINC02126 m6A sites and enhanced its stability. LINC02126 directly bound to and reduced miR-501-5p levels. Inhibition of miR-501-5p mimicked LINC02126's antitumor effects, while miR-501-5p overexpression reversed them. In vivo, LINC02126 overexpression suppressed tumor growth and decreased miR-501-5p expression.

YTHDC1 enhanced LINC02126 stability via m6A modification, and LINC02126 inhibited LUAD progression through miR-501-5p.