Circ-CCS enhances autophagy during imatinib resistance of gastrointestinal stromal tumor by regulating miR-197-3p/ATG10 signaling.

CONTEXT

Drug resistance in gastrointestinal stromal tumors (GISTs) is connected with autophagy activation. Accumulating data demonstrates the critical role of circular RNAs (circRNAs) dysregulation in this development.

AIM

To explore the possible function of hsa_circ_0092306 (circ-CCS) in GIST imatinib resistance.

MATERIALS AND METHODS

Quantitative real-time reverse transcription PCR (RT-qPCR) was used to determine the expression levels of circ-CCS and miR-197-3p. The vitality and apoptosis of cells were determined using the Cell Counting Kit-8 and TUNEL assays, respectively. Western blot analysis was used to evaluate the relative protein expression. A dual-luciferase reporter assay was used to validate the link between circ-CCS, miR-197-3p, and ATG10.

STATISTICAL ANALYSIS USED

Comparisons of two groups were analyzed using Student's t tests, and analysis of variance (ANOVA) with Tukey's post hoc test was used to compare three or more groups.

RESULTS

Circulating-CCS expression was considerably increased in the serum of imatinib-resistant GIST patients (P < 0.001). Circulating-CCS deficiency decreased cell proliferation and autophagy in GIST-882 and GIST-T1 cells, but promoted apoptosis (P < 0.05). Additionally, circ-CCS was predominantly found in the cytoplasm. Mechanically, circ-CCS targeted miR-197-3p, which may influence autophagy by downregulating ATG10, in order to modulate GIST cells' malignant tendencies. Moreover, silencing miR-197-3p reversed the effect of circ-CCS knockdown on apoptosis and autophagy in GIST cells.

CONCLUSIONS

By modulating the miR-197-3p/ATG10 axis, circ-CCS increased imatinib resistance in GIST cells, establishing a potential target for reversing medication resistance in such patients.