A Novel tiRNA-Gly-GCC-1 Promotes Progression of Urothelial Bladder Carcinoma and Directly Targets TLR4

Abstract

Background: Patients with urothelial bladder carcinoma (UBC) have a poor prognosis and a high risk of progression. Recently, tRNA-derived small RNAs (tsRNAs), a novel type of noncoding RNA, have been identified. In our previous study, we found tiRNA-Gly-GCC-1 was significantly upregulated in UBC tissue and might target the predicted target gene toll-like receptor 4 (TLR4) to play a regulatory role in UBC. Thus, the aim of this study was to identify the functional roles of tiRNA-Gly-GCC-1 and the relationship between tiRNA-Gly-GCC-1 and TLR4. Methods: After lentiviral transfection in 5637 and T24 cell lines, quantitative reverse transcription-PCR, Cell Counting Kit-8, IncuCyte ZOOM™ live cell imaging, flow cytometry, Transwell assays, scratch assay, and luciferase assay were performed. Results: The results showed down-regulation of tiRNA-Gly-GCC-1 inhibits cell proliferation, migration and invasion, promotes cell apoptosis, and affects the cell cycle. Besides, tiRNA-Gly-GCC-1 was found to inhibit TLR4 expression by directly targeting its 3′UTR. Conclusions: Our study demonstrated that tiRNA-Gly-GCC-1 promotes the progression of UBC and directly targets TLR4. This study provides novel insights for future investigations to explore the mechanisms and therapeutic targets for UBC.

A comprehensive evaluation of serum tRF‐29‐R9J8909NF5JP as a novel diagnostic and prognostic biomarker for gastric cancer

“…progression of bladder cancer with downregulation inhibiting cell proliferation, migration, and invasion, promoting apoptosis, and affecting the cell cycle. 31 Similarly, Chen et al concluded that tRFphe-GAA-031 and tRF-VAL-TCA-002 are significantly upregulated in colorectal cancer (CRC) tissues and could be used as potential biomarkers and targets for intervention. 32 In the present study, we screened three tsRNAs in the tsRFun database according to Log2 Today, most studies have demonstrated that the action mechanisms of tsRNAs influence cancer progression.…”

“…39 According to previous studies, some tsRNAs can influence cancer progression through the protein sponge mechanism. 12,31 Tao et al…”

“…12 Qin et al showed that tiRNA-Gly-GCC-1 inhibited the expression of TLR4 by targeting its 3′ UTR, thereby promoting the progression of bladder cancer. 31 Therefore, we predicted potential target genes downstream of tRF-29-R9J8909NF5JP using three databases and predicted their functions and pathways using GO and KEGG databases. It will help to further investigate the mechanism of tRF-29-R9J8909NF5JP in GC in the future.…”

“…Nowadays, a growing number of studies have found that tsRNAs are dysregulated in various cancers and that their expression is variable during cancer development and staging. For example, Qin et al showed that tiRNA‐Gly‐GCC‐1influences the progression of bladder cancer with downregulation inhibiting cell proliferation, migration, and invasion, promoting apoptosis, and affecting the cell cycle 31 . Similarly, Chen et al concluded that tRF‐phe‐GAA‐031 and tRF‐VAL‐TCA‐002 are significantly upregulated in colorectal cancer (CRC) tissues and could be used as potential biomarkers and targets for intervention 32 .…”

Yeni Küçük Kodlamayan RNA Sınıfı: tiRNA

“…Benzer bir araştırmada Qin ve ark. [71] tanımlanan yeni bir tiRNA-Gly-GCC-1'in, mesane kanserinin ilerlemesinde teşvik edici bir görevinin toll bezeri resöptörü TLR4'ü hedefleyerek yaptıgını ortaya çıkarmışlardır. tiRNA-Gly-GCC-1'in aşagı regülasyonu sonucunda ise, hücre çoğalması göçünü ve apoptozu teşvik edebileceğini gösterdiler.…”