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SNRPB-mediated regulation of DDX39A splicing promotes ovarian cancer progression by regulating α6 integrin subunit expression

Oncogene volume 44, pages 2170–2185 (2025)Cite this article

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Abstract

Dysfunction or aberrant expression of DEAD-box RNA helicases might play a role in the initiation and progression of human cancers. Nevertheless, the key regulator and underlying molecular mechanism have yet to be fully elucidated in ovarian cancer. This study identified DDX39A as one of the prominently upregulated genes in ovarian cancer through a systematic analysis of RNA helicase expression profiles using the CPTAC and TCGA ovarian cancer datasets. High expression of DDX39A was confirmed in paraffin-embedded ovarian cancer samples. Specifically, elevated DDX39A expression was found to be associated with poor overall survival in ovarian cancer patients. Antisense oligonucleotide-mediated DDX39A silencing led to a decrease in the proliferation capacity of a CDX model and a PDX model. Furthermore, DDX39A expression is regulated by the splicing factor SNRPB. SNRPB depletion or DDX39A knockdown induced the retention of DDX39A introns 6 and 8 to generate the noncoding transcript DDX39A-209, which yielded premature termination codons and resulted in nonsense-mediated RNA decay and decreased expression of the DDX39A protein. DDX39A silencing reduced the proliferative and metastatic capacities of SNRPB-overexpressing cells, indicating that DDX39A mediates the oncogenic function of SNRPB in ovarian cancer cells. In addition, RNA-Seq data analysis revealed that DDX39A promotes the proliferation and metastasis of ovarian cancer cells through the regulation of exon skipping of ITGA6 to produce the oncogenic ITGA6A transcript. These findings suggest that the SNRPB/DDX39A/ITGA6 axis plays critically important role in the progression of ovarian cancer, which increases our understanding of the role of DEAD-box RNA helicases and provides a viable therapeutic target for ovarian cancer.

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Fig. 1: DDX39A is identified as an important DEAD-box RNA helicase in ovarian cancer.
Fig. 2: DDX39A increases growth rate and metastasis capacity of ovarian cancer cells.
Fig. 3: ASO-mediated DDX39A silencing inhibits the proliferation capacity of ovarian cancer in vitro and in vivo.
Fig. 4: DDX39A was identified as the key downstream target of SNRPB through RNA-seq in ovarian cancer cells.
Fig. 5: SNRPB silencing induces DDX39A intron 6 and 8 retentions in ovarian cancer cells.
Fig. 6: Silencing of DDX39A decreased the oncogenic effects of SNRPB overexpression in ovarian cancer cells.
Fig. 7: ITGA6 was identified as a critical downstream target gene of DDX39A through RNA-seq of ovarian cancer cells.
Fig. 8: DDX39A mediates ITGA6 exon skipping in ovarian cancer cells.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank American Journal Experts (AJE) for English language editing.

Funding

This work was supported by Natural Science Foundation of Shandong Province (ZR2023MH183, ZR2022QH074), the Tai-Shan Scholar Program of Shandong Province (No. ts20070743).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji’nan, Shandong Province, China

    Yingwei Li

  2. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji’nan, Shandong Province, China

    Zhongshao Chen, Yuehan Gao, Qianqian Gao, Yingying Pu, Huimin Xiao, Cunzhong Yuan, Shi Yan, Ning Yang & Beihua Kong

  3. Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong Province, China

    Yanling Liu

  4. Department of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, Shangdong, China

    Yuchao Diao

  5. Department of Obstetrics and Gynecology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China

    Li Guo

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Contributions

Conception and design: YW L. Methodology: YW L. Acquisition of data: YW L, ZC, YL. Analysis and interpretation of data: YW L, ZC, YL. Administrative, technical, or material support: YW L, ZC, YL, YG, HX, QG, YP, LG, YD, CY, SY, NY. Study supervision: YW L, BK. Writing, review, and/or revision of the manuscript: YW L Final approval: All authors.

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Correspondence to Yingwei Li or Beihua Kong.

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The authors declare no competing interests.

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All methods in this study were performed in accordance with the relevant guidelines and regulations. Ethics Committee at Qilu Hospital of Shandong University approved the study (KYLL-202407-059-1). The Nude mouse xenograft assay and PDX model assay were approved by the Shandong University Animal Care and Use Committee (24045). Informed consent was obtained from all participants.

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Li, Y., Chen, Z., Gao, Y. et al. SNRPB-mediated regulation of DDX39A splicing promotes ovarian cancer progression by regulating α6 integrin subunit expression. Oncogene 44, 2170–2185 (2025). https://doi.org/10.1038/s41388-025-03386-0

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