Abstract
BackgroundRecently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer.MethodsQuantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice.ResultstRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth.ConclusionstRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.
Highlights
Gastric cancer is one of the most common digestive tract tumors worldwide [1]
By upregulating and downregulating the expression of tRNA-derived fragments (tRFs)-5026a in gastric cancer cells, we found that tRF-506a regulated the growth of gastric cancer cells through the Tensin homolog deleted on chromosome ten gene (PTEN)/phosphatidylinositide 3-kinase (PI3K)/ Protein kinase B (AKT) signaling pathway
Low expression of tRF-5026a is observed in gastric cancer tissues and cells To detect tRF-5026a levels by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), specific amplification primers for tRF-5026a were designed that spanned both the tRF-5026a and adaptor sequences
Summary
Gastric cancer is one of the most common digestive tract tumors worldwide [1]. Early-stage gastric cancer patients do not typically experience discomfort or any symptoms. Most gastric cancer patients are diagnosed with middle- and late-stage disease, resulting in a 5-year postoperative survival rate of as low as 25%. The 5-year postoperative survival rate for early-stage gastric cancer is 90–95% [2]. MicroRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) have been demonstrated to play a role in the occurrence, development, and prognosis of gastric cancer [3,4,5,6,7]. The role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer
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