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tRF-3013b inhibits gallbladder cancer proliferation by targeting TPRG1L
Lu Zou1,2,3, Yang Yang1,2,3, Biyu Zhou4
1Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
Background:
tRNA-derived fragments (tRFs) are newly discovered noncoding RNAs and regulate tumor progression via diverse molecular mechanisms. However, the expression and biofunction of tRFs in gallbladder cancer (GBC) have not been reported yet.
Methods:
The expression of tRFs in GBC was detected by tRF and tiRNA sequencing in GBC tissues and adjacent tissues. The biological function of tRFs was investigated by cell proliferation assay, clonal formation assay, cell cycle assay, and xenotransplantation model in GBC cell lines. The molecular mechanism was discovered and verified by transcriptome sequencing, fluorescence in situ hybridization (FISH), target gene site prediction, and RNA binding protein immunoprecipitation (RIP).
Results:
tRF-3013b was significantly downregulated in GBC compared with para-cancer tissues. Decreased expression of tRF-3013b in GBC patients was correlated with poor overall survival. Dicer regulated the production of tRF-3013b, and its expression was positively correlated with tRF-3013b in GBC tissues. Functional experiments demonstrated that tRF-3013b inhibited GBC cell proliferation and induced cell-cycle arrest. Mechanically, tRF-3013b exerted RNA silencing effect on TPRG1L by binding to AGO3, and then inhibited NF-κB. TPRG1L overexpression could rescue the effects of tRF-3013b on GBC cell proliferation.
Conclusions:
This study indicated that Dicer-induced tRF-3013b inhibited GBC proliferation by targeting TPRG1L and repressed NF-κB, pointing to tRF-3013b as a novel potential therapeutic target of GBC.
Insights
This study reveals that tRNA-derived fragment-3013b (tRF-3013b) is downregulated in gallbladder cancer, inhibiting tumor growth by targeting TPRG1L and repressing NF-κB. This suggests tRF-3013b is a potential therapeutic target for GBC.
Area of Science:
- Oncology
- Molecular Biology
- Noncoding RNA Research
Background:
- tRNA-derived fragments (tRFs) are emerging noncoding RNAs with roles in tumor progression.
- The expression and function of tRFs in gallbladder cancer (GBC) remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression, function, and molecular mechanisms of tRFs in GBC.
- To identify potential therapeutic targets for GBC based on tRFs.
Main Methods:
- tRF and tiRNA sequencing to detect tRF expression in GBC tissues.
- Functional assays including cell proliferation, clonal formation, cell cycle, and xenotransplantation models.
- Transcriptome sequencing, FISH, and RIP to elucidate molecular mechanisms.
Main Results:
- tRF-3013b was significantly downregulated in GBC and correlated with poor survival.
- Dicer regulates tRF-3013b production; its expression inhibits GBC cell proliferation and induces cell cycle arrest.
- tRF-3013b silences TPRG1L, subsequently inhibiting NF-κB signaling.
Conclusions:
- Dicer-induced tRF-3013b inhibits GBC proliferation by targeting TPRG1L and repressing NF-κB.
- tRF-3013b represents a novel potential therapeutic target for gallbladder cancer.
