Identification and potential mechanism of a novel gastric cancer suppressor tRF-24- 6VR8K09LE9

Abstract

Abstract Background One of the most common gastrointestinal tumors is gastric cancer (GC), which has a high lethality and a poor prognosis. Traditional markers are relatively limited in detecting the development and prognosis of GC. Recently, it was discovered that mature tRNAs, which are expressed differently in a variety of malignancies, give rise to a novel class of tRNA-derived small RNAs (tsRNAs). Methods In this study, we investigated the role of short RNAs produced from tRNA in GC and possible therapeutic uses. edgeR was used to screen the differentially expressed tsRNAs from the TCGA database and quantitative real-time PCR (qRT-PCR) was used to verify the levels of tsRNAs in GC samples. Sanger sequencing, agarose gel electrophoresis, and freeze-thaw experiments have been utilized to assess its stability in serum samples. The association between tRF-24-6VR8K09LE9 and clinicopathological features was investigated by the Chi-square test. Diagnostic effectiveness is assessed by Receiver operating characteristic (ROC) curves. Furthermore, mechanistic studies were performed to explore tRF-24-6VR8K09LE9 regulating the malignant progression of GC through PI3K/AKT signaling pathway. Results tRF-24-6VR8K09LE9 down-regulated in GC was confirmed by detecting serum samples from 114 patients with gastric cancer, 40 patients with gastritis and 100 normal controls. The Chi-square test displayed that tRF-24-6VR8K09LE9 was highly related to differentiation grade (P = 0.029), T-stage (P = 0.036), lymph node status (P = 0.036), TNM staging (P < 0.0001), and neurological/vascular invasion (P = 0.033).The ROC curve indicated that tRF-24-6VR8K09LE9 is more effective than the current diagnostic markers for GC. Furthermore, mechanistic studies verified that tRF-24-6VR8K09LE9 affected the malignant progression of GC through the PI3K/AKT signaling pathway. Conclusions tRF-24-6VR8K09LE9 can be served as a molecular marker for early GC auxiliary diagnosis. Over-expression of tRF-24-6VR8K09LE9 inhibits the malignant progression of GC, which may provide a new strategy for the adjuvant treatment of GC.