tRF-Gln-CTG-7 promotes AML cell growth and survival through AGGF1 and is associated with poor prognosis

Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, characterized by marked biological heterogeneity and an unfavorable prognosis. tRNA-derived small RNAs (tsRNAs) are involved in tumor progression, but their roles in AML remain poorly understood, so we investigated tRF-Gln-CTG-7 in AML. tsRNA microarray screening was used to analyze differential expression between AML patients and healthy controls and tRF-Gln-CTG-7 was identified for further investigation. Further, the effects of tRF-Gln-CTG-7 inhibition on cell growth and apoptosis were evaluated in AML cell lines using a CCK-8 assay, and Western blotting. The molecular mechanism was explored using RNA-seq, luciferase reporter assays, and rescue experiments. tRF-Gln-CTG-7 was elevated in AML patients compared with healthy controls, and high expression was closely associated with shorter overall survival. Inhibition of tRF-Gln-CTG-7 suppressed AML cell growth and induced apoptosis in OCI-AML2 and MOLM-13. tRF-Gln-CTG-7 inhibition increased AGGF1 mRNA and protein levels. AGGF1 knockdown rescued the growth arrest and apoptosis induced by tRF-Gln-CTG-7 inhibition. tRF-Gln-CTG-7 promotes AML cell growth by suppressing AGGF1 through AGO2-associated targeting of its 3′ UTR. tRF-Gln-CTG-7 expression is increased in AML and may promote AML cell growth by suppressing AGGF1 . tRF-Gln-CTG-7 may represent a potential prognostic biomarker and therapeutic target for AML.