ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma.
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Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
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16 citing papers in PubMed.
- Disruption of the SNRPF-DDX24-E2F4 Feedback Loop Uncouples Splicing and Transcriptional Regulation to Suppress Ovarian Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancer.Oncogene · 2026Article
- TRIM26-mediated NKRF degradation drives Osimertinib resistance through SNRPD2-dependent stress granule formation in lung adenocarcinoma.Cell death & disease · 2026Article
- Role of DDX39A in modulating the tumor progression and radiosensitivity in esophageal squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Article
- Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SNRPD2-mediated regulation of DDX39B splicing promotes endometrial cancer progression by suppressing the activation of CTSC cryptic exons.Cell death & disease · 2026Article
- Transcriptomics and single-cell RNA sequencing uncover prognostic characteristics and immune regulatory mechanisms of lactylation in cervical cancer.BioImpacts : BI · 2026Article
- Integrated analysis uncoversInternational journal of medical sciences · 2026Article
- N6-Methyladenosine-Modified circNEK11 Promotes Hepatocellular Carcinoma Progression via the miR-1236-3p/GPX2 Axis.Cancer science · 2025Article
- RBM17 promotes hepatocellular carcinoma progression by regulating lipid metabolism and immune microenvironment: implications for therapeutic targeting.Cell death discovery · 2025Article
- hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.Nature communications · 2025Article
- Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- SNRPD2-dependency Fuels an Oncogenic Alternative Splicing Repertoire Driving Disease Aggressiveness in Glioma.Cancer genomics & proteomicsArticle
- A Potential miR-1246-5p-H3K27ac-NOL12 Regulatory Axis and Its Putative Tumour-Promoting Function in Hepatocellular Carcinoma.IET systems biologyArticle
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Authors and funding
32 authors.
Cunjie ChangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Lina LiMedical Molecular Biology Laboratory, Medical College, Jinhua University of Vocational Technology, Jinhua, 321016, P.R. China.
Ling SuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Fan YangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Quanxiu ZhaSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Mengqing SunSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Lin TaoSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Menglan WangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Kangli SongSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Liangyu JiangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Haojin GaoSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Yexin LiangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Chao XuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Caiyu YongSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Minmin WangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Jiacheng HuangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Jing LiuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Weiwei JinSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Wenyuan LvSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Heng DongSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Qian LiSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.ORCID 0000-0002-2560-5730
Fangtian BuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Shuanghong YanSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Haoxiang QiSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Shujuan ZhaoSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Yingshuang ZhuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Yu WangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Junping ShiSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.
Yiting QiaoThe First Affiliated Hospital, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310003, P. R. China.
Jian XuHepatobiliary and Liver transplantation Department of Hainan Digestive Disease Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, P. R. China.
Benoit ChabotDépartement de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
Jianxiang ChenSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, P. R. China.ORCID 0000-0002-8193-191X
Funding
Fundamental Research Funds for the Central Universities 226-2023-00107Innovative Research Group Project of the National Natural Science Foundation of ChinaNational Natural Science Foundation of China 82072646National Natural Science Foundation of China 82273953National Natural Science Foundation of China 82372664National Natural Science Foundation of China 82373888National Outstanding Youth Science Fund Project of National Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province LR21H160001Natural Science Foundation of Zhejiang Province LY21H160043"Pioneer" and "Leading Goose" R&D Program of Zhejiang Province 2022C03004Research Project of Jinan Microecological Biomedicine Shandong Laboratory JNL-2022029CStart-up Grant of HZNU 4125C50220204014the Key Project of Social Development of Jinhua Science and Technology Bureau of Zhejiang Province 2023-3-165Zhejiang Traditional Chinese Medicine Administration GZY-ZJ-KJ-24045
Abstract
RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer-suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin.
Indexed as
Carcinoma, HepatocellularDEAD-box RNA HelicasesIntronsLiver NeoplasmsRNA SplicingSpliceosomesAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred BALB CMice, NudeProto-Oncogene Proteins c-mycRibonucleoproteins, Small NuclearDDX39A protein, humanDEAD-box RNA HelicasesMYC protein, humanProto-Oncogene Proteins c-mycRibonucleoproteins, Small NuclearsnRNP Core ProteinsSNRPD2 protein, humandigitoxinMYC signalingRNA splicingSm proteins
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