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 m1G...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-1αstability through the enhancement of cellular oxygen content.Moreover,our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α.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.展开更多
基金This work was supported by the National Key Research and Development Program of China(Nos.2020YFA0113003 and 2018YFC1004803)the Fundamental Research Funds for the Central Universities.
文摘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-1αstability through the enhancement of cellular oxygen content.Moreover,our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α.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.
