The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

Zhu, Linwen; Li, Zhe; Yu, Xiuchong; Ruan, Yao; Shen, Yijing; Shao, Yongfu; Zhang, Xinjun; Ye, Guoliang; Guo, Junming

doi:10.1186/s13287-021-02497-1

Cited by 46 publications

(46 citation statements)

References 51 publications

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“…Since previous studies demonstrated tsRNAs could exert biological mechanisms in a manner similar to miRNAs by binding to the 3’-UTR of target genes, 29 we predicted target genes of tiRNA-Val-CAC-001 and explored its roles using bioinformatics method. We analyzed the target genes of tiRNA-Val-CAC-001 with GO and KEGG enrichment analysis.…”

Section: Discussionmentioning

confidence: 99%

A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer

Zheng¹,

Liu²,

Zhu³

et al. 2022

CMAR

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Background Gastric cancer (GC) is a common type of gastrointestinal tumor in the world. Transfer RNA (tRNA) derived fragments (tsRNAs) implicate various cancers, but their roles in GC remain unclear. Our study aimed to investigate the potential biological functions and molecular mechanisms of tsRNAs in GC. Methods Differentially expressed tsRNAs were identified using high-throughput sequencing. The expression levels of tsRNAs were validated in 62 paired GC tissues and adjacent normal tissues using RT-qPCR. In vitro functional assays were used to evaluate the influences of tsRNAs on GC cells. The potential mechanisms underlying tsRNAs were explored using bioinformatics analysis,RT-qPCR, RNA immunoprecipitation assays and Western blot. Results We found that tiRNA-Val-CAC-001 was downregulated in GC tissues and cells, and demonstrated that tiRNA-Val-CAC-001 was a tsRNA sheared from mature tRNA-Val and mainly localized in the cytoplasm. tiRNA-Val-CAC-001 overexpression inhibited metastasis and proliferation but promoted apoptosis of GC cells; nevertheless, tiRNA-Val-CAC-001 knockdown increased metastasis and proliferation and reduced apoptosis ( P <0.05). GO and KEGG analyses indicated tiRNA-Val-CAC-001 may exert its effects via Wnt/β-catenin signaling pathway by targeting LRP6. Following experiments showed that tiRNA-Val-CAC-001 could downregulated the protein levels of LRP6 and β-catenin, but up-regulated p-β-catenin, which confirmed the findings in bioinformatics analysis. Conclusion In conclusion, tiRNA-Val-CAC-001 works as a cancer suppressor in GC by targeting LRP6 via Wnt/β-catenin signaling pathway. tiRNA-Val-CAC-001 may serve as a therapy target and a biomarker of GC in the future. Key Points tiRNA-Val-CAC-001 is downregulated in gastric cancer tissues and cell lines, tiRNA-Val-CAC-001 has potential to become a novel diagnostic biomarker in gastric cancer, and tiRNA-Val-CAC-001 regulates gastric cancer cells by targeting LRP6.

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Section: Discussionmentioning

confidence: 99%

A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer

Zheng¹,

Liu²,

Zhu³

et al. 2022

CMAR

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“…To check the influence of miR‐203a‐3p mimic/inhibitor and siMAP3K1 on the process of the cell cycle of TPC‐1 and KTC‐1 cells, cell cycle evaluation was carried out using the PI/RNase staining reagent (Becton), and were detected with a flow cytometer (Beckman Coulter) as previously described. 18 …”

Section: Methodsmentioning

confidence: 99%

MicroRNA‐203a‐3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy

Dai

Zhang

et al. 2022

Clinical Laboratory Analysis

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Background Papillary thyroid carcinoma (PTC) grows slowly but has a great risk of metastasis. MicroRNAs are well known as vital tumor‐related gene regulators. In PTC, the role of miR‐203a‐3p and the underlying mechanisms remain not completely understood. Methods We conducted CCK8 assay, wound healing assay, transwell experiment and flow cytometry analyses to investigate the function of miRNA‐203a‐3p. The interaction of miRNA‐203a‐3p with its gene MAP3K1 was characterized by quantitative real‐time polymerase chain reaction, western blotting and luciferase assay. Results We found that the levels of miRNA‐203a‐3p were statistically decreased in PTC tissues. When mimics were delivered to TPC‐1 and KTC‐1 cells to upregulate miR‐203a‐3p, it was observed that cell proliferation, metastatic abilities and cell cycle process were prevented but cell apoptosis was enhanced. Furthermore, we proved the interaction between MAP3K1 and miR‐203a‐3p. Intriguingly, similar to miR‐203a‐3p mimics, siMAP3K1 showed a tumor‐suppressive effect, and this effect could be reversed when miR‐203a‐3p was simultaneously inhibited. Finally, selected autophagy‐linked proteins such as LC3 Beclin‐1 were detected and found to be increased when miR‐203a‐3p was upregulated or MAP3K1 was inhibited. Conclusion Overall, miR‐203a‐3p inhibits the oncogenic characteristics of TPC‐1 and KTC‐1 cells via suppressing MAP3K1 and activating autophagy. Our findings might enrich the understanding and the therapeutic strategies of PTC.

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“…A better understanding of tRF biomarkers may help elucidate possible biomarkers. For example, tRF-5026a was shown to regulate PTEN/PI3/AKT signaling pathway and decrease gastric cancer cell proliferation, suggesting that tRF-5026 may be used as a biomarker for gastric cancer ( Zhu et al, 2021 ).…”

Section: Trna-derived Fragments and Cancer Developmentmentioning

confidence: 99%

tRNA Function and Dysregulation in Cancer

Gupta

Malkin

Huang

2022

Front. Cell Dev. Biol.

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Transfer RNA (tRNA) is a central component of protein synthesis and plays important roles in epigenetic regulation of gene expression in tumors. tRNAs are also involved in many cell processes including cell proliferation, cell signaling pathways and stress response, implicating a role in tumorigenesis and cancer progression. The complex role of tRNA in cell regulation implies that an understanding of tRNA function and dysregulation can be used to develop treatments for many cancers including breast cancer, colon cancer, and glioblastoma. Moreover, tRNA modifications including methylation are necessary for tRNA folding, stability, and function. In response to certain stress conditions, tRNAs can be cleaved in half to form tiRNAs, or even shorter tRNA fragments (tRF). tRNA structure and modifications, tiRNA induction of stress granule formation, and tRF regulation of gene expression through the repression of translation can all impact a cell’s fate. This review focuses on how these functions of tRNAs, tiRNA, and tRFs can lead to tumor development and progression. Further studies focusing on the specific pathways of tRNA regulation could help identify tRNA biomarkers and therapeutic targets, which might prevent and treat cancers.

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The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

Cited by 46 publications

References 51 publications

A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer

A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer

MicroRNA‐203a‐3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy

tRNA Function and Dysregulation in Cancer

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