Emerging studies have proved that
tRNA-derived fragments (tRFs) play vital roles in
tumor metastasis; however, the function of tRFs in
gastric cancer (GC) remains largely unclear. We investigated the role of tRF-24-V29K9UV3IU in growth and
metastasis of GC using a xenograft mouse model. Differential gene expression downstream of tRF-24-V29K9UV3IU was identified by transcriptome sequencing, and interaction was then verified by a dual
luciferase reporter and
RNA immunoprecipitation. MKN-45 cells were also used to explore the biological functions of tRF-24-V29K9UV3IU in vitro. Here, knockdown of tRF-24-V29K9UV3IU promoted
tumor growth and
metastasis of GC in vivo. The expression of tRF-24-V29K9UV3IU and
E-cadherin (epithelial cell marker) was down-regulated in
tumors of mice following tRF-24-V29K9UV3IU knockdown, whereas the mesenchymal cell markers
N-cadherin and
vimentin displayed an opposite trend. Transcriptome sequencing identified 87 differentially expressed genes (DEGs) down-regulated in the tRF-24-V29K9UV3IU-overexpressed groups compared with the control group. Among them,
G-protein-coupled receptor 78 (GPR78), the most significantly down-regulated DEG, was also predicted to be a target of tRF-24-V29K9UV3IU. Moreover, tRF-24-V29K9UV3IU could function as a
miRNA-like fragment and bind to AGO2 and directly silence GPR78 expression by complementing with the 3'-untranslated region of the GPR78
mRNA. Functionally, overexpression of tRF-24-V29K9UV3IU significantly suppressed proliferation, migration, and invasion and promoted apoptosis of MKN-45 cells, whereas GPR78 attenuated these effects. Therefore, our data suggest that tRF-24-V29K9UV3IU functions as a
miRNA-like fragment to suppress GPR78 expression and thus inhibit GC progression. These observations suggest that the tRF-24-V29K9UV3IU/GPR78 axis serves as a potential therapeutic target in GC.