Abstract
BackgroundGastric cancer (GC) is one of the most common cancers in the world. Due to the lack of specific symptoms, more than 80% of patients are diagnosed as the advanced stage with a high mortality rate, so the early diagnosis of GC is incredibly essential. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors.MethodUsing circRNA sequencing technology screened three pairs of GC and adjacent tissues, and circRNAs with significant expression differences were screened out. The circular structure and characteristics of circPTPN22 were determined by RT-qPCR, agarose gel electrophoresis, Sanger sequencing, RNase R, and actinomycin D assays. Cell Counting Kit‐8, colony formation, Transwell, Wound healing, tumor formation in mice and western blotting assays were used to detect the effects of circPTPN22 on the proliferation, invasion, migration, tumor growth of GC cells in vitro and protein expression.ResultCircPTPN22 is up-regulated and positively correlated with metastasis in GC tissues, cells, and plasma. RT-qPCR results showed that circPTPN22 had good diagnostic efficacy and could be used to predict the prognosis of GC patients. In vitro and vivo experiments showed that the downregulation of circPTPN22 could inhibit cell proliferation, migration, and invasion through the epithelial-mesenchymal transformation (EMT) pathway. CircPTPN22 may regulate GC progression through the competitive binding of miRNAs.ConclusionCircPTPN22 can be used as a potential diagnostic and prognostic marker for GC and can inhibit cell proliferation and metastasis through the competitive binding of miRNA to inhibit the EMT pathway.
Highlights
Gastric cancer (GC) is one of the most common cancers globally, and the third-largest cause of cancer-related deaths after lung and liver cancer [1]
About one-eighth of the genes expressed in humans can produce detectable circRNAs, and their expression level is more than ten times of the corresponding linear messenger RNA level [4, 6]
To determine the circRNA with the highest correlation with GC metastasis, Quantitative reverse transcription PCR (RT-qPCR) was used to verify the difference of expression levels of the three circRNAs in 20 pairs of GC metastatic tissues and their adjacent nontumor tissues, the results show that circPTPN22 showed the most obvious difference in expression and the highest expression in the metastatic GC specimens (Fig. 1d)
Summary
Gastric cancer (GC) is one of the most common cancers globally, and the third-largest cause of cancer-related deaths after lung and liver cancer [1]. CircRNAs are expressed in different tissues and at different developmental stages [7]. With the development of research, circRNAs have been considered as microRNA (miRNA) sponge, protein bait, RNA splicing regulator, parent gene transcription regulator, and potential protein translation template [9, 10]. CircRNAs have demonstrated advantages as biomarkers for tumor diagnosis and treatment due to its biological properties and functions. A growing body of evidence indicates that circRNAs is closely related to human diseases, especially cancer. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors
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