The potential roles of circular RNA (circRNA) in gastrointestinal stromal tumors (GISTs) can be identified as a valuable marker in the diagnosis, therapy, and prognosis of patients, according to a new study published in the Journal of Immunology Research.

GISTs originate from the interstitial cells of Cajal and have a steady rate of increase every year. Various tumor markers contribute to the diagnosis and prediction of these tumors, and research on more reliable biomarkers can significantly improve their management and prognosis.

Researchers explored the expression of circRNA in GISTs and its role in the regulation of these tumors. circRNA is an endogenous noncoding RNA, which is more stable against exonuclease in comparison to linear RNA. Although the biological function of a majority of circRNAs is still unclear, various studies have shown its role in the regulation of certain tumors.


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In an attempt to assess the role of circRNA and mRNA dysregulation in GISTs, this study created a circRNA-miRNA-mRNA network. By analyzing 2 groups of circRNAs and mRNAs, 7 differentially expressed circRNAs and 12 differentially expressed genes (DEGs) were identified.

Four key DEGs were defined (ATP1A2, PLN, KCNMA1, and SCNN1B) and a protein-protein interaction network was created. The role of circTBC1D4/hsa-miR-590-5p/PLN axes in stromal tumors was explored using the Circular RNA Interactome and the TargetScanHuman databases.

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Out of the 4 key DEGs, the results of the study suggest that phospholamban (PLN) and ATP1A1 might play a vital role in upregulating GIST. ATP1A2 hydrolyzes ATP which regulates the activity of pacemaker cells through the influx of exogenous calcium and release of calcium from the endoplasmic reticulum which generates an inward pacing current.

As the interstitial cells of Cajal exist in the stands and peripheral nerve to the muscularis propria gastrointestinal pacemaker cells, the team hypothesized that ATP has an upregulating role in GISTs. The effect of ATP on pacing current can hence be inhibited by clearance of exogenous calcium and prevention of calcium uptake by the endoplasmic reticulum. Furthermore, PLN regulates calcium reuptake during muscle relaxation, and blocking this mechanism may affect the progress of the GIST.

While various studies have confirmed the unusual expression of circRNA and the regulatory role of the circRNA-miRNA-mRNA network in upregulating tumors, there are few reports on their role in GISTs.

Reference

Chunyan-Zou, Yanpeng-He, Changshun-Xie, et al. Potential value of circular RNA circTBC1D4 in gastrointestinal stromal tumorsJ Immunol Res. 2022;9019097:1-15. doi:10.1155/2022/9019097