A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer.
A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer.
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DOI：
10.2147/cmar.s363629
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发表时间：
2022
影响因子：
3.3
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中科院分区：
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胃癌是世界上常见的胃肠道肿瘤类型。转移RNA(TRNA)衍生片段(TsRNAs)与多种癌症有关，但它们在胃癌中的作用尚不清楚。本研究旨在探讨tsRNAs在胃癌中的潜在生物学功能及其分子机制。高通量测序鉴定差异表达的tsRNAs。采用RT-qPCR方法检测62例配对的胃癌组织和癌旁正常组织中tsRNAs的表达水平。采用体外功能测定的方法评价tsRNAs对GC细胞的影响。通过生物信息学分析、RT-qPCR、RNA免疫沉淀分析和Western印迹分析，探讨了tsRNAs的可能机制。我们发现tiRNA-Val-CAC-001在胃癌组织和细胞中表达下调，证明tiRNA-Val-CAC-001是从成熟tRNA-Val剪切而来的tsRNA，主要定位于细胞质。TiRNA-Val-CAC-001过表达抑制了GC细胞的转移和增殖，但促进了细胞的凋亡；而TiRNA-Val-CAC-001过表达则增加了转移和增殖，减少了细胞凋亡(P<；0.05)。GO和KEGG分析表明，tiRNA-Val-CAC-001可能通过Wnt/β-catenin信号通路靶向LRP6发挥作用。随后的实验表明，TiRNA-Val-CAC-001能够下调LRP6和β-连环蛋白的蛋白水平，而上调p-β-连环蛋白的表达水平，这在生物信息学分析中得到了证实。综上所述，tiRNA-Val-CAC-001通过Wnt/β-catenin信号通路靶向LRP6，在胃癌中发挥抑癌作用。TiRNA-Val-CAC-001可能成为未来胃癌的治疗靶点和生物标志物。TiRNA-Val-CAC-001在胃癌组织和细胞系中表达下调，tiRNA-Val-CAC-001有可能成为一种新的胃癌诊断生物标志物，而tiRNA-Val-CAC-001通过靶向LRP6来调节胃癌细胞。
Gastric cancer (GC) is a common type of gastrointestinal tumor in the world. Transfer RNA (tRNA) derived fragments (tsRNAs) implicate various cancers, but their roles in GC remain unclear. Our study aimed to investigate the potential biological functions and molecular mechanisms of tsRNAs in GC. Differentially expressed tsRNAs were identified using high-throughput sequencing. The expression levels of tsRNAs were validated in 62 paired GC tissues and adjacent normal tissues using RT-qPCR. In vitro functional assays were used to evaluate the influences of tsRNAs on GC cells. The potential mechanisms underlying tsRNAs were explored using bioinformatics analysis,RT-qPCR, RNA immunoprecipitation assays and Western blot. We found that tiRNA-Val-CAC-001 was downregulated in GC tissues and cells, and demonstrated that tiRNA-Val-CAC-001 was a tsRNA sheared from mature tRNA-Val and mainly localized in the cytoplasm. tiRNA-Val-CAC-001 overexpression inhibited metastasis and proliferation but promoted apoptosis of GC cells; nevertheless, tiRNA-Val-CAC-001 knockdown increased metastasis and proliferation and reduced apoptosis (P<0.05). GO and KEGG analyses indicated tiRNA-Val-CAC-001 may exert its effects via Wnt/β-catenin signaling pathway by targeting LRP6. Following experiments showed that tiRNA-Val-CAC-001 could downregulated the protein levels of LRP6 and β-catenin, but up-regulated p-β-catenin, which confirmed the findings in bioinformatics analysis. In conclusion, tiRNA-Val-CAC-001 works as a cancer suppressor in GC by targeting LRP6 via Wnt/β-catenin signaling pathway. tiRNA-Val-CAC-001 may serve as a therapy target and a biomarker of GC in the future. tiRNA-Val-CAC-001 is downregulated in gastric cancer tissues and cell lines, tiRNA-Val-CAC-001 has potential to become a novel diagnostic biomarker in gastric cancer, and tiRNA-Val-CAC-001 regulates gastric cancer cells by targeting LRP6.