PMID- 36632750 OWN - NLM STAT- MEDLINE DCOM- 20230209 LR - 20230209 IS - 1862-1783 (Electronic) IS - 1673-1581 (Print) IS - 1673-1581 (Linking) VI - 24 IP - 1 DP - 2023 Jan 15 TI - Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1alpha pathways. PG - 50-63 LID - 1673-1581(2023)01-0050-14 [pii] LID - 10.1631/jzus.B2200224 [doi] AB - Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1alpha stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1alpha. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy. FAU - Zhao, Qiong AU - Zhao Q AD - Department of Genetics, and Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. AD - Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, Zhejiang University, Hangzhou 310058, China. FAU - Zhang, Luwen AU - Zhang L AD - Department of Genetics, and Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. AD - Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, Zhejiang University, Hangzhou 310058, China. FAU - He, Qiufen AU - He Q AD - Department of Genetics, and Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. AD - Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, Zhejiang University, Hangzhou 310058, China. FAU - Chang, Hui AU - Chang H AD - Department of Genetics, and Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. AD - Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, Zhejiang University, Hangzhou 310058, China. FAU - Wang, Zhiqiang AU - Wang Z AD - Department of Genetics, and Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. AD - Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, Zhejiang University, Hangzhou 310058, China. FAU - Cao, Hongcui AU - Cao H AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. FAU - Zhou, Ying AU - Zhou Y AD - Xiangshan Hospital of TCM Medical and Health Group, Ningbo 315700, China. FAU - Pan, Ruolang AU - Pan R AD - Zhejiang Provincial Key Laboratory of Cell-Based Drug and Applied Technology Development, Hangzhou 311121, China. yechency@zju.edu.cn, panrl@zju.edu.cn. FAU - Chen, Ye AU - Chen Y AD - Department of Genetics, and Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. yechency@zju.edu.cn. AD - Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, Zhejiang University, Hangzhou 310058, China. yechency@zju.edu.cn. LA - eng LA - chi GR - 2020YFA0113003 and 2018YFC1004803/the National Key Research and Development Program of China/ PT - Journal Article TT - 靶向TRMT5抑制HIF-1alpha信号通路调控肝癌进程. PL - China TA - J Zhejiang Univ Sci B JT - Journal of Zhejiang University. Science. B JID - 101236535 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - EC 2.1.1.228 (TRMT5 protein, human) RN - EC 2.1.1.- (tRNA Methyltransferases) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/genetics/pathology MH - Cell Hypoxia MH - Cell Line, Tumor MH - Gene Expression Regulation, Neoplastic MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism MH - *Liver Neoplasms/genetics/pathology MH - Signal Transduction/genetics MH - *tRNA Methyltransferases/genetics/metabolism PMC - PMC9837375 OTO - NOTNLM OT - Hepatocellular carcinoma (HCC) OT - Hypoxia-inducible factor-1alpha (HIF-1alpha) OT - Transfer RNA (tRNA) OT - tRNA methyltransferase 5 (TRMT5) EDAT- 2023/01/13 06:00 MHDA- 2023/01/14 06:00 PMCR- 2023/01/15 CRDT- 2023/01/12 03:33 PHST- 2023/01/12 03:33 [entrez] PHST- 2023/01/13 06:00 [pubmed] PHST- 2023/01/14 06:00 [medline] PHST- 2023/01/15 00:00 [pmc-release] AID - 1673-1581(2023)01-0050-14 [pii] AID - 1673-1581（2023）01-0050-14 [pii] AID - 10.1631/jzus.B2200224 [doi] PST - ppublish SO - J Zhejiang Univ Sci B. 2023 Jan 15;24(1):50-63. doi: 10.1631/jzus.B2200224.