Clinical diagnostic values of transfer RNA-derived fragment tRF-19-3L7L73JD and its effects on the growth of gastric cancer cells

Abstract

Background and aim: Medicine has made great progress, but gastric cancer is still one of the most common malignant tumors worldwide. tRNA-derived fragments (tRFs), a type of small non-coding RNA, have been found to play important roles in cancers. Due to an abundance of modifications, tRFs have the potential to serve as cancer biomarkers. However, the relationship between tRFs and gastric cancer is still largely unclear. We have identified a new tRF, tRF-19-3L7L73JD, found to be expressed at a lower level in gastric cancer patients than healthy controls. Our study aims to explore the diagnostic value of tRF-19-3L7L73JD screening in gastric cancer and to investigate its effects on the growth of gastric cancer cells. Methods: Using quantitative reverse transcription-polymerase chain reaction, we identified tRF-3L7L73JD as differentially expressed in plasma from gastric cancer patients compared to healthy controls. We measured tRF-3L7L73JD levels in plasma from 40 gastric cancer patients and healthy controls. Furthermore, we tested another cohort containing 89 gastric cancer patients and 98 healthy controls to validate our findings. Next, we analyzed the relationship between levels of tRF-19-3L7L73JD in plasma and clinicopathological data of gastric cancer patients, and then evaluated the effects of tRF-19-3L7L73JD on gastric cancer cell growth. Cell proliferation was measured by the Cell Counting Kit-8 and clone formation experiments after transfer with tRF-19-3L7L73JD mimics. The changes in cell migration ability were explored through the scratch and Transwell experiments. Finally, we explored changes in apoptosis and cell cycle by flow cytometry. Results: tRF-19-3L7L73JD showed lower expression in the tested gastric cancer patients. In the validation cohort tRF-19-3L7L73JD was also expressed at low levels in the pre-operative plasma group compared with healthy plasma and post-operative plasma groups. Additionally, a comparison of gastric cancer cell lines with normal gastric epithelial cell lines produced the same result. We found that tRF-19-3L7L73JD expression in patients was related to tumor size. The area under the curve (AUC) was 0.6230, with sensitivity and specificity of 0.4045 and 0.7959, respectively. Cellular function studies revealed that tRF-19-3L7L73JD inhibited cell proliferation and migration, induced apoptosis, and arrested cells at G0/G1 phases, suggesting it may suppress the development of gastric cancer. Conclusion:The results suggest that tRF-19-3L7L73JD may be useful as a biomarker of gastric cancer.

tRNA‐derived fragments in gastric cancer: Biomarkers and functions

“…Seven studies 11 , 29 , 33 , 34 , 35 , 36 , 37 used a genome‐wide discovery approach with high throughput sequencing or small RNA sequencing to identify candidate tRFs, which were then validated in an independent cohort using qRT‐PCR. Using this approach, three of these three studies 11 , 32 , 33 selected a panel of tRFs to distinguish GC from normal controls. Table 1 summarizes the study's characteristics.…”

“…Shen et al found that tRF‐19‐3L7L73JD suppresses cell proliferation as well as migration, induces apoptosis, and arrests cells at the G0/G1 phases, implying inhibitory roles in GC development. 32 …”

Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer

“…Some sncRNAs not only can promote cell proliferation as a carcinogen, but also inhibit the development of cancer as an inhibitor. For instance, tRF-19-3L7L73JD derived from tRNA-Val-AAC can inhibit the development of gastric cancer by blocking cell proliferation in G0/G1 phase 61. Downregulation of SNORA42 can inhibit non-small cell lung cancer cell proliferation by inducing p53-dependent apoptosis 62.…”

“…sncRNAs can be detected not only in tumour tissues but also in circulating blood. According to the unique expression pattern between cancer and normal specimens and the correlation with clinicopathological features, sncRNAs have become an ideal biomarker platform for cancer diagnosis 52 61 80–83. For example, U6 snRNA was significantly upregulated in cervical cancer, and the degree of upregulation was positively correlated with the stage of cancer 84.…”

Transfer RNA-derived small RNA: an emerging small non-coding RNA with key roles in cancer

“…Another study found that the tRF-3017A derived from tRNA Val−TAC can combine with AGO protein to regulate the expression of cancer suppressor gene NELL2, which promotes migration of GC cells and metastasis of lymph nodes in GC patients, and has the effect of facilitating GC malignant progression [ 29 ]. Besides, the expression of tRF-19-3L7L73JD was decreased in GC, which could block the GC cell cycle in the G0/G1 phase, induce apoptosis, inhibit cell proliferation and migration, and thus inhibit the malignant progression of GC [ 78 ]. Moreover, tsRNAs can also influence the progression of GC by regulating signaling pathways.…”