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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>DCST1-AS1 promotes RCC progression by modulation of the miR-582-5p/HMGB2 axis, and may thus have clinical potential in treating RCC.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Chuanjing Dai,
  • Jiannan Hu,
  • Xiong Tian,
  • Hanxi Zhou,
  • Zhenyu Yang,
  • Shunqiao Jin,
  • Jingmin Zheng

摘要

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.