LncRNA SNHG5/miR‐363‐3p/USP28 Axis Promotes Lung Adenocarcinoma Progression Through Enhancing β‐Catenin Stabilization

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, accounting for approximately 50% of global lung cancer‐related mortality, which underscores the urgent need for identifying novel biomarkers and therapeutic targets. Long noncoding RNAs (lncRNAs) have been increasingly recognized as pivotal regulators in cancer development; however, the specific function of lncRNA small nucleolar RNA host gene 5 (SNHG5) in LUAD remained unclear. This study aimed to investigate the clinical significance, biological roles, and molecular mechanisms of SNHG5 in LUAD pathogenesis. Through integrated bioinformatics analysis and experimental validation, we found that SNHG5 was significantly upregulated in LUAD tissues and cell lines. Functional in vitro and in vivo assays—including gain‐/loss‐of‐function studies, luciferase reporter assays, RNA immunoprecipitation, co‐immunoprecipitation, and tumor xenograft models—demonstrated that SNHG5 promoted malignant phenotypes by acting as a competing endogenous RNA (ceRNA) for miR‐363‐3p. This sponge activity elevated the expression of ubiquitin‐specific peptidase 28 (USP28), which in turn stabilized β‐catenin and activated oncogenic signaling. Rescue experiments confirmed the functional importance of the SNHG5/miR‐363‐3p/USP28/β‐catenin axis. In conclusion, these results indicate that SNHG5 drives LUAD progression through a novel ceRNA mechanism, highlighting its potential as both a prognostic biomarker and a therapeutic target.