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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.

SUBMITTER: Shen Y

PROVIDER: S-EPMC8100793 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Context: Papillary thyroid cancer (PTC) is the most common thyroid cancer with dramatically increasing worldwide. Accurate diagnosis is crucial to avoid unnecessary overtreatment for low-risk patients, but the currently available markers are still insufficient. tRNA-derived fragments (tRFs) are emerging as a new class of small non-coding RNAs due to their potential roles as novel biomarkers and therapeutic targets in cancer. However, their involvement in papillary thyroid carcinoma (PTC) is still unclear. Objectives: This study was performed to identify differentially expressed tRFs in PTC and investigate the role of serum tRFs to discriminate PTC from nodular goiters (NGs).Methods and Materials: tRF expression profiles were measured in pooled sera from patients with PTCs (n=6), NGs (n=6) and healthy subjects (n=6) using high-throughput sequencing (cohort1). One selected tRF candidate was validated in the same individual samples (cohort1) by qRT-PCR. The confirmed tRF was further validated in a larger second cohort including patients with PTCs (n=30), NGs (n=20) and healthy individuals (n=18).Results: Our sequencing results showed that circulating tRFs were differentially expressed in patients with PTC compared with those with NG and healthy people. After the validation in individual samples, tRF-Pro-AGG-018 was confirmed as differentially elevated in serum samples of patients with PTC. These results were further confirmed in a larger second cohort. Moreover, tRF-Pro-AGG-018 exhibited good diagnostic performance with a sensitivity of 0.7222 and a specificity of 0.8846 for PTC and it was associated with several targeted genes of PTC. Conclusions: Our study identified that the serum tRFs were differentially expressed in PTC compared with NG and healthy individuals. Notably, circulating tRF-Pro-AGG-018 was found to have a significant elevation in patients with PTC and exhibited good diagnostic performance with relatively high sensitivity and specificity for PTC. Our findings suggest tRFs might serve as novel circulating biomarkers in predicting patients with PTC, which may prevent unnecessary thyroid surgeries for low-risk and benefit from optimal

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

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