tRNA-derived fragment tRFLys-CTT-010 promotes triple-negative breast cancer progression by regulating glucose metabolism via G6PC
tRNA-derived fragment tRFLys-CTT-010 promotes triple-negative breast cancer progression by regulating glucose metabolism via G6PC
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DOI：
10.1093/carcin/bgab058
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发表时间：
2021-07-03
期刊：
影响因子：
4.7
通讯作者：
Zhou, Ping
中科院分区：
文献类型：
--
作者：
Zhu, Ping;Lu, Jingjing;Zhou, Ping
tRNA-derived fragments (tRFs) are a novel class of small non-coding RNAs whose biological roles are not well defined. Here, using multiple approaches, we investigated its role in human triple-negative breast cancer (TNBC). Our genome-wide transcriptome analysis of small non-coding RNAs revealed that tRF(Lys-CTT-010) was significantly increased in human TNBC. It promoted TNBC proliferation and migration. It also closely associated with starch and sucrose metabolism pathways (Kyoto Encyclopedia of Genes and Genomes analysis) and positively regulated the expression of glucose-6-phosphatase catalytic subunit (G6PC), one of the related genes in the pathway. G6PC, a complex of glucose-6-phosphatase in gluconeogenesis and glycogenolysis, is upregulated in human TNBC samples. Further studies demonstrated that overexpression of G6PC in tRF(Lys-CTT-010) inhibitor-transfected TNBC cell lines can reverse malignant biological behavior and knockdown of G6PC in TNBC cell lines inhibited tumor progression and reversed the oncogenic function of tRF(Lys-CTT-010). In addition, tRF(Lys-CTT-010) interacted with G6PC to regulate cellular lactate production and glycogen consumption, resulting in cell survival and proliferation. Thus, fine-tuning glucose metabolism and the tRF(Lys-CTT-010)/G6PC axis may provide a therapeutic target for TNBC treatment.[GRAPHICS].
