Global profile of tRNA-derived small RNAs in gastric cancer patient plasma and identification of tRF-33-P4R8YP9LON4VDP as a new tumor suppressor

BackgroundGastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.MethodsQuantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.ResultsThe expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (P<0.0001).ConclusionsSerum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Serum hsa_tsr016141 as a Kind of tRNA-Derived Fragments Is a Novel Biomarker in Gastric Cancer

Liang

et al. 2021

“…High-throughput sequencing revealed tsRNA signatures in cancers, indicating that like microRNAs, tsRNAs may have an oncogenic or tumor-suppressor function in tumors ( 34 , 54 ). In the study of cellular function, it has been found that tRF-33-P4R8YP9LON4VDP could proliferate GC cells in vitro and might be a potential site for targeted therapy ( 55 ). In breast cancer research, it was also found that the runt-related transcription factor 1 (Runx 1) can reverse the excessive proliferation of tumor cells induced by ts-112 ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Role of Serum tRF-31-U5YKFN8DYDZDD as a Novel Diagnostic Biomarker in Gastric Cancer (GC)

Huang

Zhang

et al. 2021

BackgroundGastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC.Materials and MethodsFirst of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy.ResultsThe expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers.ConclusionsThe expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.

“…Additionally, Shen et al. found that levels of tRF-33-P4R8YP9LON4VDP were significantly downregulated in plasma samples of gastric patients and that this tsRNA inhibited the proliferation of gastric carcinoma cells ( 93 ).…”

Section: Biological Processes Correlated With Tsrnasmentioning

confidence: 99%

“…Thus, these data established a prognostic model for bladder cancer based on the expression levels of specific tsRNA. Recently, researchers have also discovered multiple tsRNA signatures in gastric cancer, papillary thyroid cancer, and other malignancies ( 38 , 91 , 93 ). The literature research on this matter highlighted the need for a broader validation of tsRNAs as sensitive biomarkers for cancer diagnosis and prognosis.…”

Section: Biological Processes Correlated With Tsrnasmentioning

confidence: 99%

Transfer RNA-Derived Small RNAs: Novel Regulators and Biomarkers of Cancers

2022

Transfer RNA-derived small RNAs (tsRNAs) are conventional non-coding RNAs (ncRNAs) with a length between18 and 40 nucleotides (nt) playing a crucial role in treating various human diseases including tumours. Nowadays, with the use of high-throughput sequencing technologies, it has been proven that certain tsRNAs are dysregulated in multiple tumour tissues as well as in the blood serum of cancer patients. Meanwhile, data retrieved from the literature show that tsRNAs are correlated with the regulation of the hallmarks of cancer, modification of tumour microenvironment, and modulation of drug resistance. On the other side, the emerging role of tsRNAs as biomarkers for cancer diagnosis and prognosis is promising. In this review, we focus on the specific characteristics and biological functions of tsRNAs with a focus on their impact on various tumours and discuss the possibility of tsRNAs as novel potential biomarkers for cancer diagnosis and prognosis.