DCST1-AS1 promotes renal cell carcinoma progression via regulating the miR-582-5p/HMGB2 axis.

BACKGROUND: Renal cell carcinoma (RCC) represents between 80 and 90% of primary renal cancers. While long non-coding RNAs (lncRNAs) are documented to modulate RCC development, their biological functions remain poorly understood. METHODS: RNA sequencing data from 541 RCC and 71 adjacent normal tissues were downloaded from TCGA database. Kaplan-Meier survival, ROC curve, and clinicopathologic analyses were used to examine the prognostic value of the lncRNA DCST1-AS1 in RCC. The levels of DCST1-AS1 in RCC tissues and cell lines were assessed using quantitative PCR, and its subcellular localization was examined using fluorescence in situ hybridization and RNA nuclear-cytoplasmic separation assays. The functional role of DCST1-AS1 was investigated through a series of in vitro experiments including CCK-8, colony formation, wound-healing, and Transwell assays, as well as in RCC xenograft mice. The targets of DCST1-AS1 were examined using RNA-pull down, luciferase reporter, and RNA immunoprecipitation assays, while Western blotting and immunofluorescence were utilized for investigation of the potential involvement of the PI3K/AKT/GSK-3β axis. RESULTS: DCST1-AS1 levels were observed to be elevated in both RCC tissues and cell lines, with raised levels linked to advanced tumor stage, pTNM stage, and unfavorable patient prognosis. DCST1-AS1 knockdown reduced proliferation, migration, and cell cycle progression in RCC cells. Conversely, DCST1-AS1 overexpression promoted both tumorigenesis and metastasis in xenograft mice. Mechanistically, DCST1-AS1 enhanced HMGB2 expression by sponging miR-582-5p. Moreover, DCST1-AS1 overexpression stimulated the PI3K/AKT/GSK-3β axis and nucelar translocation of β-catenin. Further functional experiments confirmed that LY294002, a PI3K-specific inhibitor, could attenuate the tumor-promoting effects induced by DCST1-AS1 overexpression. CONCLUSIONS: DCST1-AS1 promotes RCC progression by modulation of the miR-582-5p/HMGB2 axis, and may thus have clinical potential in treating RCC.