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Hsa_circular RNA_0001013 exerts oncogenic effects in gastric cancer through the microRNA-136-TWSG1 axis.

BACKGROUND
Gastric cancer (GC) is one of the leading malignancies of the digestive system. Circular RNAs (circRNAs) are well-established to play critical regulatory roles in GC development. The current study sought to explore the effects and regulatory mechanism of circ_0001013 in the course of GC.


METHODS
First, differential circRNAs and related mechanisms in GC were predicted by microarray analysis. Circ_0001013, microRNA (miR)-136, and TWSG1 expression patterns were subsequently detected in GC clinical samples and cells using RT-qPCR. The relationship among circ_0001013, miR-136, and TWSG1 was further assessed by dual-luciferase reporter assay, biotin-coupled probe pull-down assay, and biotin-coupled miRNA capture. Based on gain- and loss-of-function assays, GC cell proliferation, migration, invasion, and the cell cycle and apoptosis were also measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, scratch test, Transwell assay, and flow cytometry, respectively. Moreover, the effect of circ_0001013 on tumor growth was detected by tumor xenografting in nude mice.


RESULTS
Circ_0001013 was predicted to be up-regulated in GC by microarray profiling, which was confirmed by RT-qPCR detection in GC tissues and cells. miR-136 was poorly expressed, and TWSG1 was highly expressed in GC tissues. Mechanistically, circ_0001013 bound to miR-136, which negatively targeted TWSG1 in the GC cells. Silencing circ_0001013 or TWSG1 or over-expressing miR-136 led to decreased GC cell proliferation, migration, invasion, and cell cycle arrest and enhanced apoptosis. Furthermore, silencing circ_0001013 resulted in diminished TWSG1 expression and inhibited transplanted tumor growth in the nude mice.


CONCLUSION
Collectively, our findings indicated that circ_0001013 increased TWSG1 expression by binding to miR-136, thereby exerting oncogenic effects in GC.