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 tRFLys-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 tRFLys-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 tRFLys-CTT-010. In addition, tRFLys-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 tRFLys-CTT-010/G6PC axis may provide a therapeutic target for TNBC treatment.

中文翻译：

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tRNA 衍生片段 tRFLys-CTT-010 通过 G6PC 调节葡萄糖代谢促进三阴性乳腺癌进展。

tRNA 衍生片段 (tRFs) 是一类新型的小型非编码 RNA，其生物学作用尚未明确。在这里，我们使用多种方法研究了它在人类三阴性乳腺癌 (TNBC) 中的作用。我们对小型非编码 RNA 的全基因组转录组分析显示，人类 TNBC 中的 tRFLys-CTT-010 显着增加。它促进了 TNBC 的扩散和迁移。它还与淀粉和蔗糖代谢途径密切相关（京都基因百科全书和基因组分析），并正向调节葡萄糖-6-磷酸酶催化亚基 (G6PC) 的表达，这是该途径中相关基因之一。G6PC 是一种葡萄糖-6-磷酸酶在糖异生和糖原分解中的复合物，在人类 TNBC 样本中上调。进一步的研究表明，在转染 tRFLys-CTT-010 抑制剂的 TNBC 细胞系中过表达 G6PC 可以逆转恶性生物学行为，并且在 TNBC 细胞系中敲低 G6PC 可抑制肿瘤进展并逆转 tRFLys-CTT-010 的致癌功能。此外，tRFLys-CTT-010 与 G6PC 相互作用以调节细胞乳酸产生和糖原消耗，从而导致细胞存活和增殖。因此，微调葡萄糖代谢和 tRFLys-CTT-010/G6PC 轴可能为 TNBC 治疗提供治疗靶点。tRFLys-CTT-010 与 G6PC 相互作用以调节细胞乳酸产生和糖原消耗，从而导致细胞存活和增殖。因此，微调葡萄糖代谢和 tRFLys-CTT-010/G6PC 轴可能为 TNBC 治疗提供治疗靶点。tRFLys-CTT-010 与 G6PC 相互作用以调节细胞乳酸产生和糖原消耗，从而导致细胞存活和增殖。因此，微调葡萄糖代谢和 tRFLys-CTT-010/G6PC 轴可能为 TNBC 治疗提供治疗靶点。