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

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

  • J Transl Med. 2025 Nov 26;23(1):1352. doi: 10.1186/s12967-025-07403-4.
Chuanjing Dai 1,  Jiannan Hu 1,  Xiong Tian 1,  Hanxi Zhou 1,  Zhenyu Yang 1,  Shunqiao Jin 2,  Jingmin Zheng 3
Affiliations

Affiliations

  • 1 Department of Public Experimental Platform, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, China.
  • 2 Department of Dermatology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China.
  • 3 Department of Public Experimental Platform, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, China. [email protected].
PMID: 41299565 DOI: 10.1186/s12967-025-07403-4
Abstract

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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12967-025-07403-4.

Keywords

DCST1-AS1; HMGB2; Renal cell carcinoma; Tumorigenesis; miR-582-5p.

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