ArticleSignal transduction and targeted therapy2025
The cryptic lncRNA-encoded microprotein TPM3P9 drives oncogenic RNA splicing and tumorigenesis.
Article in Signal transduction and targeted therapy, 2025. 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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Who cites it
16 citing papers in PubMed.
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
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- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- The long non-coding RNA-encoded microprotein MKKS3 drives colorectal cancer chemoresistance.Experimental & molecular medicine · 2026Article
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- Reannotation of Public Transcriptomic Data Identifies Candidate lncRNAs and Putative Regulatory Networks in Rhabdomyosarcoma.Biomedicines · 2026Article
- Long Non-Coding RNAs in Pathogenesis of Renal Cell Carcinoma: Epigenetic Regulation, Signaling Pathways, and Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Retinoic Acid and Long Noncoding RNAs Crosstalk: Implications for Neuronal Differentiation and Diseases.Molecular neurobiology · 2026Review
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- Preliminary exploration of the putative function of SF3A2 in clear cell renal cell carcinoma.Molecular medicine reports · 2026Article
- Elevated GPX3 expression in endometriosis: implications for pathogenesis and immune cell infiltration.European journal of medical research · 2026Article
- Urinary proteomic profiling reveals diagnostic biomarkers and regulatory networks in myasthenia gravis.BMC neurology · 2026Article
- BPA: a BERT-based priority annotation strategy for assessing the rationality of aquatic algal protein sequences.Briefings in bioinformatics · 2025Article
- Long Non-Coding TP73-AS1: A Potential Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2025Review
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- Multi-omics landscape of alternative splicing in diffuse midline glioma reveals immune- and neural-driven subtypes with implications for spliceosome-targeted therapy.Frontiers in immunology · 2025Article
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14 authors.
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Abstract
Emerging evidence demonstrates that cryptic translation from RNAs previously annotated as noncoding might generate microproteins with oncogenic functions. However, the importance and underlying mechanisms of these microproteins in alternative splicing-driven tumor progression have rarely been studied. Here, we show that the novel protein TPM3P9, encoded by the lncRNA tropomyosin 3 pseudogene 9, exhibits oncogenic activity in clear cell renal cell carcinoma (ccRCC) by enhancing oncogenic RNA splicing. Overexpression of TPM3P9 promotes cell proliferation and tumor growth. Mechanistically, TPM3P9 binds to the RRM1 domain of the splicing factor RBM4 to inhibit RBM4-mediated exon skipping in the transcription factor TCF7L2. This results in increased expression of the oncogenic splice variant TCF7L2-L, which activates NF-κB signaling via its interaction with SAM68 to transcriptionally induce RELB expression. From a clinical perspective, TPM3P9 expression is upregulated in cancer tissues and is significantly correlated with the expression of TCF7L2-L and RELB. High TPM3P9 expression or low RBM4 expression is associated with poor survival in patients with ccRCC. Collectively, our findings functionally and clinically characterize the "noncoding RNA"-derived microprotein TPM3P9 and thus identify potential prognostic and therapeutic factors in renal cancer.
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