Evidence map›Paper›PMID 39865075›Full record

ArticleSignal transduction and targeted therapy2025

The cryptic lncRNA-encoded microprotein TPM3P9 drives oncogenic RNA splicing and tumorigenesis.

Kun Meng, Yuying Li, Xiaoyi Yuan, Hui-Min Shen, Li-Ling Hu, Danya Liu, Fujin Shi, Dandan Zheng, Xinyu Shi, Nengqiao Wen and 4 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Kun Meng *MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Yuying Li *MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Xiaoyi Yuan *MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Hui-Min Shen *Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Li-Ling HuMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Danya LiuMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Fujin ShiMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Dandan ZhengMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Xinyu ShiMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Nengqiao WenDepartment of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.
Yun CaoDepartment of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.ORCID 0000-0002-3001-0395
Yun-Long PanThe First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China.
Qing-Yu HeMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China. tqyhe@email.jnu.edu.cn.
Chris Zhiyi ZhangMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China. zhangzy@jnu.edu.cn.ORCID 0000-0002-1944-8281

Funding

Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2022A1515012388
6 · The paper itself

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.

Indexed as

CarcinogenesisCarcinoma, Renal CellKidney NeoplasmsRNA-Binding ProteinsRNA, Long NoncodingRNA SplicingTropomyosinAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceTranscription Factor 7-Like 2 ProteinRBM4 protein, humanRNA-Binding ProteinsRNA, Long NoncodingTranscription Factor 7-Like 2 ProteinTropomyosin

Identifiers

PMID39865075
PMCPMC11770092

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.