PMID- 36401185 OWN - NLM STAT- MEDLINE DCOM- 20221122 LR - 20221122 IS - 1689-1392 (Electronic) IS - 1425-8153 (Print) IS - 1425-8153 (Linking) VI - 27 IP - 1 DP - 2022 Nov 18 TI - tRF-3013b inhibits gallbladder cancer proliferation by targeting TPRG1L. PG - 99 LID - 10.1186/s11658-022-00398-6 [doi] LID - 99 AB - 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-kappaB. 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-kappaB, pointing to tRF-3013b as a novel potential therapeutic target of GBC. CI - (c) 2022. The Author(s). FAU - Zou, Lu AU - Zou L AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Yang, Yang AU - Yang Y AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Zhou, Biyu AU - Zhou B AD - Department of Plastic and Reconstructive Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China. FAU - Li, Weijian AU - Li W AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Liu, Ke AU - Liu K AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Li, Guoqiang AU - Li G AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Miao, Huijie AU - Miao H AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Song, Xiaoling AU - Song X AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665, Kongjiang Road, Shanghai, 200092, China. FAU - Yang, Jiahua AU - Yang J AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Geng, Yajun AU - Geng Y AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. FAU - Li, Maolan AU - Li M AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. limaolan6@163.com. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. limaolan6@163.com. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. limaolan6@163.com. FAU - Bao, Runfa AU - Bao R AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. baorunfa@yeah.net. AD - Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665, Kongjiang Road, Shanghai, 200092, China. baorunfa@yeah.net. FAU - Liu, Yingbin AU - Liu Y AUID- ORCID: 0000-0001-6110-0185 AD - Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. laoniulyb@shsmu.edu.cn. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China. laoniulyb@shsmu.edu.cn. AD - Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. laoniulyb@shsmu.edu.cn. LA - eng GR - 81874181/National Natural Science Foundation of China/ GR - 32130036/National Natural Science Foundation of China/ GR - 20JC1419101/Shanghai Municipal Science and Technology Major Project/ GR - 21YF1428700/Shanghai Sailing Program/ GR - 20ZR1435200/Natural Science Foundation of Shanghai/ PT - Journal Article DEP - 20221118 PL - England TA - Cell Mol Biol Lett JT - Cellular & molecular biology letters JID - 9607427 RN - 0 (NF-kappa B) SB - IM MH - Humans MH - *Gallbladder Neoplasms/genetics/metabolism/pathology MH - Gene Expression Regulation, Neoplastic MH - NF-kappa B/metabolism MH - In Situ Hybridization, Fluorescence MH - Cell Proliferation PMC - PMC9673407 OTO - NOTNLM OT - Cell cycle OT - Cell proliferation OT - Gallbladder cancer OT - tRNA-derived fragments COIS- All authors declare that they have no competing interests. EDAT- 2022/11/20 06:00 MHDA- 2022/11/23 06:00 PMCR- 2022/11/18 CRDT- 2022/11/19 00:02 PHST- 2022/07/09 00:00 [received] PHST- 2022/10/25 00:00 [accepted] PHST- 2022/11/19 00:02 [entrez] PHST- 2022/11/20 06:00 [pubmed] PHST- 2022/11/23 06:00 [medline] PHST- 2022/11/18 00:00 [pmc-release] AID - 10.1186/s11658-022-00398-6 [pii] AID - 398 [pii] AID - 10.1186/s11658-022-00398-6 [doi] PST - epublish SO - Cell Mol Biol Lett. 2022 Nov 18;27(1):99. doi: 10.1186/s11658-022-00398-6.