PMID- 37365531 OWN - NLM STAT- MEDLINE DCOM- 20230628 LR - 20230701 IS - 1689-1392 (Electronic) IS - 1425-8153 (Print) IS - 1425-8153 (Linking) VI - 28 IP - 1 DP - 2023 Jun 26 TI - A novel tyrosine tRNA-derived fragment, tRF(Tyr), induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA. PG - 49 LID - 10.1186/s11658-023-00463-8 [doi] LID - 49 AB - BACKGROUND: Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. METHODS: We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT-PCR) of 60 paired samples. The tyrosine-tRNA derivative tRF(Tyr) was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRF(Tyr) in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRF(Tyr) in LSCC. RESULTS: tRF(Tyr) was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRF(Tyr) significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRF(Tyr) could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells. CONCLUSIONS: Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRF(Tyr) in LSCC. tRF(Tyr) could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC. CI - (c) 2023. The Author(s). FAU - Zhao, Rui AU - Zhao R AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Yang, Zhenming AU - Yang Z AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Zhao, Bo AU - Zhao B AD - School of Forestry, Northeast Forestry University, Harbin, China. FAU - Li, Wenjing AU - Li W AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Liu, Yaohui AU - Liu Y AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Chen, Xiaoxue AU - Chen X AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Cao, Jing AU - Cao J AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Zhang, Jiarui AU - Zhang J AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Guo, Yan AU - Guo Y AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Xu, Licheng AU - Xu L AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Wang, Jinpeng AU - Wang J AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Sun, Yanan AU - Sun Y AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Liu, Ming AU - Liu M AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. liumingorl@qq.com. FAU - Tian, Linli AU - Tian L AUID- ORCID: 0000-0002-8934-1607 AD - Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. tianlinli78@163.com. LA - eng GR - 82072987/National Natural Science Foundation of China/ GR - 82273332/National Natural Science Foundation of China/ GR - 82103164/National Natural Science Foundation of China/ GR - 82173209/National Natural Science Foundation of China/ GR - LH2019H014/Natural Science Foundation of Heilongjiang Province/ GR - 2020M681115/China Postdoctoral Science Foundation/ GR - YQ2022H008/Youth Project of Heilongjiang Natural Science Foundation/ PT - Letter DEP - 20230626 PL - England TA - Cell Mol Biol Lett JT - Cellular & molecular biology letters JID - 9607427 RN - EC 1.1.1.27.- (Lactate Dehydrogenase 5) RN - 33X04XA5AT (Lactic Acid) RN - 63231-63-0 (RNA) RN - 9014-25-9 (RNA, Transfer) RN - 42HK56048U (Tyrosine) SB - IM MH - Humans MH - Squamous Cell Carcinoma of Head and Neck/genetics MH - Lactate Dehydrogenase 5/genetics/metabolism MH - *Lactic Acid MH - RNA MH - RNA, Transfer/genetics/metabolism MH - Carcinogenesis/genetics MH - *Head and Neck Neoplasms/genetics MH - Tyrosine/genetics/metabolism MH - Gene Expression Regulation, Neoplastic PMC - PMC10291753 OTO - NOTNLM OT - LDHA OT - LSCC OT - Lactate OT - tRFTyr OT - tsRNAs COIS- The authors declare that they have no conflicts of interest. EDAT- 2023/06/27 01:06 MHDA- 2023/06/28 06:42 PMCR- 2023/06/26 CRDT- 2023/06/26 23:36 PHST- 2023/02/26 00:00 [received] PHST- 2023/05/29 00:00 [accepted] PHST- 2023/06/28 06:42 [medline] PHST- 2023/06/27 01:06 [pubmed] PHST- 2023/06/26 23:36 [entrez] PHST- 2023/06/26 00:00 [pmc-release] AID - 10.1186/s11658-023-00463-8 [pii] AID - 463 [pii] AID - 10.1186/s11658-023-00463-8 [doi] PST - epublish SO - Cell Mol Biol Lett. 2023 Jun 26;28(1):49. doi: 10.1186/s11658-023-00463-8.