Accounting for the majority of primary kidney tumors, renal cell carcinoma (RCC) constitutes roughly 80–90% of cases. Despite evidence that long non-coding RNAs (lncRNAs) impact RCC development, their exact mechanisms of action remain largely undefined. RNA sequencing data from 541 renal cell carcinoma (RCC) cases and 71 matched normal adjacent tissues were obtained from the TCGA database. The prognostic significance of the long non-coding RNA DCST1-AS1 in RCC was evaluated through Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and correlations with clinicopathological features. Expression levels of DCST1-AS1 were measured in RCC tissues and cell lines via quantitative real-time PCR. Its subcellular distribution was determined using fluorescence in situ hybridization and nuclear-cytoplasmic fractionation experiments. The biological functions of DCST1-AS1 were explored through various in vitro assays, such as CCK-8 proliferation, colony formation, wound-healing migration, and Transwell invasion/migration tests, along with in vivo studies in RCC xenograft mouse models. Potential interacting partners of DCST1-AS1 were identified using RNA pull-down, luciferase reporter, and RNA immunoprecipitation techniques. The possible activation of the PI3K/AKT/GSK-3β signaling pathway was assessed by Western blotting and immunofluorescence staining. DCST1-AS1 was found to be significantly upregulated in RCC tissues and cell lines, with higher expression correlating with advanced tumor stage, elevated pTNM classification, and poorer patient outcomes. Silencing DCST1-AS1 inhibited RCC cell proliferation, migration, and cell cycle progression, whereas its overexpression accelerated tumor growth and metastatic potential in xenograft mouse models. Mechanistically, DCST1-AS1 acted as a molecular sponge for miR-582-5p, leading to increased HMGB2 expression. In addition, DCST1-AS1 overexpression activated the PI3K/AKT/GSK-3β signaling pathway and promoted nuclear translocation of β-catenin. Functional assays further demonstrated that the PI3K inhibitor LY294002 could partially reverse the oncogenic effects induced by DCST1-AS1 upregulation. DCST1-AS1 contributes to the progression of renal cell carcinoma through regulation of the miR-582-5p/HMGB2 axis, highlighting its potential as a therapeutic target for RCC.
