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The lncRNA ST18-AS1 suppresses pancreatic cancer progression by enhancing ST18 mRNA stability through anchoring FUS in the cytoplasm

Oncogene volume 44, pages 2850–2863 (2025)Cite this article

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is associated with a high mortality rate and short survival time. Long noncoding RNAs (lncRNAs) play a significant role in the progression of PDAC. However, prognostic lncRNAs associated with overall survival (OS) in patients with PDAC remain elusive. RNA sequencing was used to identify differential lncRNA expression between short-term and long-term PDAC patients. We identified a novel lncRNA (ENSG00000253924), termed ST18-AS1 (ST18-associated lncRNA), that is highly expressed in the tissues of long-term PDAC patients. High ST18-AS1 expression was correlated with favorable clinical outcomes, and the upregulation of ST18-AS1 expression in PDAC cell lines suppressed cell proliferation and promoted apoptosis both in vivo and in vitro. The key downstream target regulated by ST18-AS1 was Suppression of tumorigenicity 18 (ST18). We also found that ST18 expression was lower in PDAC tissues compared to non-tumorous adjacent tissues (NATs) and that higher ST18 expression was correlated with better clinical outcomes. Accordingly, the forced expression of ST18 inhibited proliferation and promoted apoptosis in tumor cells. Mechanistic studies showed that ST18-AS1 maintained the stability of ST18 mRNA by binding to Fused in sarcoma (FUS) and anchoring FUS in the cytoplasm. Overall, we identified ST18-AS1 as a novel biomarker that inhibits PDAC cell proliferation and promotes PDAC cell apoptosis through ST18. Targeting ST18-AS1/ST18 may be a potential therapeutic strategy for treating PDAC.

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Fig. 1: Low ST18-AS1 expression is correlated with poor prognosis in patients with PDAC.
Fig. 2: ST18-AS1 inhibits the proliferation and promotes the apoptosis of PDAC cells.
Fig. 3: ST18 is a downstream target of ST18-AS1, inhibits the proliferation and promotes the apoptosis of PDAC cells.
Fig. 4: FUS is involved in the regulation of ST18 by ST18-AS1.
Fig. 5: ST18-AS1 function is partially mediated by FUS.
Fig. 6: ST18-AS1 anchors FUS in the cytoplasm and maintains ST18 mRNA stability.
Fig. 7: The ST18-AS1/FUS/ST18 signaling axis inhibits the proliferation and promotes the apoptosis of PDAC cells.

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Data availability

The datasets in this study are available from the corresponding author on reasonable request.

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Funding

This work was supported by National Nature Science Foundation of China (82370561, 82070567).

Author information

Author notes

  1. These authors contributed equally: Long Cheng, Hang Yu, Yujing Qin.

Authors and Affiliations

  1. Department of Oncology and Laparoscopy Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Long Cheng, Ruixin Wang, Tie Su, Gaoyuan Lyu, Zijian Huang, Hongtao Li, Yan Jin & Gang Wang

  2. Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Long Cheng, Ruixin Wang, Tie Su, Gaoyuan Lyu, Zijian Huang, Hongtao Li, Yan Jin, Yilong Li & Gang Wang

  3. Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Long Cheng, Ruixin Wang, Tie Su, Gaoyuan Lyu, Zijian Huang, Hongtao Li, Yan Jin, Yilong Li & Gang Wang

  4. Department of General Surgery, Harbin The First Hospital, Harbin, China

    Hang Yu

  5. Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China

    Yujing Qin

  6. Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin, China

    Yujing Qin

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Contributions

GW and YL conceived the research and designed the experiments; RW and GL illustrated the figures; LC, ZH, YJ and HL performed the experiments and analyzed the original data; LC, GW and YL analyzed and interpreted the data and assisted with the adjustments of directions; LC, HY and YQ wrote the manuscript; GL, LC and TS revised the manuscript; all authors approved the final manuscript.

Corresponding authors

Correspondence to Yilong Li or Gang Wang.

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The authors declare no competing interests.

Ethics approval and consent to participate

All methods were performed in accordance with the relevant guidelines and regulations. The animal study was approved by the Animal Experiment Ethics Committee of The First Affiliated Hospital of Harbin Medical University (Approval No. IRB-AF/SC-04/02.0), Additionally, the use of human PDAC tissues was approved by The First Affiliated Hospital of Harbin Medical University (Approval No. 2023086).

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Cheng, L., Yu, H., Qin, Y. et al. The lncRNA ST18-AS1 suppresses pancreatic cancer progression by enhancing ST18 mRNA stability through anchoring FUS in the cytoplasm. Oncogene 44, 2850–2863 (2025). https://doi.org/10.1038/s41388-025-03455-4

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