Dong Xiaolin, Fan Xirui, He Xiaoxue, Chen Sijin, Huang Weikang, Gao Jianpeng, Huang Yun, Wang Hui
Department of Neurology, The Affiliated Yan'An Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China.
Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming 650051, Yunnan, People's Republic of China.
Onco Targets Ther. 2020 Oct 28;13:10931-10943. doi: 10.2147/OTT.S266130. eCollection 2020.
Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. tRNA-derived fragments (tRFs) have been identified as potential biomarkers and cancer therapeutic targets. However, the influence of tRFs on GC remains unknown. The key tRFs were researched in vitro function and mechanism.
Here, differentially expressed tRFs between GC and paracancerous tissues were identified by small RNA sequencing, and the role of key tRF was evaluated in vitro.
Eight tRFs were significantly differentially expressed between GC tissues and adjacent tissues: five were significantly upregulated and three were downregulated in GC tissues. The results of target gene prediction and functional enrichment analysis showed that tRFs with different expressions were mainly involved in cell adhesion and connection, cell migration, wingless-type (Wnt), mitogen-activated protein kinase (MAPK), and cancer signaling pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) indicated that the expression of tRF-24-V29K9UV3IU and its target genes (CCND2, FZD3, and VANGL1) in GC tissues and cells was decreased compared with those in the control group. Importantly, overexpression of tRF-24-V29K9UV3IU inhibited cell proliferation, migration and invasion, while promoted cell apoptosis of GC cells.
This study suggests that tRF-24-V29K9UV3IU may hinder GC tumor progression by inhibiting cell proliferation, migration, invasion, while promoting cell apoptosis by regulating the Wnt signaling pathways.
胃癌（GC）是全球癌症相关死亡的第二大主要原因。转运RNA衍生片段（tRFs）已被确定为潜在的生物标志物和癌症治疗靶点。然而，tRFs对GC的影响仍不清楚。对关键tRFs的体外功能和机制进行了研究。
在此，通过小RNA测序鉴定了GC组织和癌旁组织之间差异表达的tRFs，并在体外评估了关键tRF的作用。
GC组织和相邻组织之间有8种tRFs显著差异表达：5种在GC组织中显著上调，3种下调。靶基因预测和功能富集分析结果表明，表达不同的tRFs主要参与细胞粘附和连接、细胞迁移、无翅型（Wnt）、丝裂原活化蛋白激酶（MAPK）和癌症信号通路。定量实时聚合酶链反应（qRT-PCR）表明，与对照组相比，GC组织和细胞中tRF-24-V29K9UV3IU及其靶基因（CCND2、FZD3和VANGL1）的表达降低。重要的是，tRF-24-V29K9UV3IU的过表达抑制了GC细胞的增殖、迁移和侵袭，同时促进了细胞凋亡。
本研究表明，tRF-24-V29K9UV3IU可能通过抑制细胞增殖、迁移、侵袭来阻碍GC肿瘤进展，同时通过调节Wnt信号通路促进细胞凋亡。
