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

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 26, 2025

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 in alternative splicing-driven tumor progression have rarely been studied. Here, we show novel protein TPM3P9, encoded by lncRNA tropomyosin 3 pseudogene 9, exhibits activity clear cell renal carcinoma (ccRCC) enhancing RNA splicing. Overexpression TPM3P9 promotes proliferation growth. Mechanistically, binds to RRM1 domain splicing factor RBM4 inhibit RBM4-mediated exon skipping transcription TCF7L2. This results increased expression splice variant TCF7L2-L, which activates NF-κB signaling via its interaction SAM68 transcriptionally induce RELB expression. From a clinical perspective, is upregulated cancer tissues significantly correlated TCF7L2-L RELB. High or low associated poor survival patients ccRCC. Collectively, our findings functionally clinically characterize "noncoding RNA"-derived microprotein thus identify potential prognostic therapeutic factors cancer.

Language: Английский

Emerging Role of Endogenous Peptides Encoded by Non-coding RNAs in Cancer Biology

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 10, P. 231 - 241

Published: Oct. 30, 2024

Language: Английский