1. Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China.
2. Department of Clinical Laboratory, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210009, China.
3. Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China.
#These authors contributed equally to this work.
Circular RNAs (circRNAs), a new kind of non-coding RNAs, have gradually been proved to be critical regulators of gene expression; however, the underlying mechanisms still need to be elaborated. In the present study, we investigated the role of hsa-circ-0007766 in gastric carcinoma (GC). Quantitative real-time PCR was applied to detect the differential expression levels of circRNA, miRNAs, and mRNAs in human tissues and specific cell lines. GC cell lines were transiently transfected with siRNA. Then the proliferation, migration, and invasion assays were performed to evaluate the effect of hsa-circ-0007766 in GC cell lines. Fluorescence in situ hybridization, RNA pulldown assay was used to confirm the location of hsa-circ-0007766 and its relationship with miR-1233-3p. Luciferase reporter assay was then conducted to verify the interaction between miR-1233-3p and GDF15. Interestingly, we found that hsa-circ-0007766 was highly expressed in human GC tissues and GC cell lines. Knock-down of hsa-circ-0007766 inhibited cell proliferation, migration, invasion, and down-regulated the expression of GDF15. Moreover, hsa-circ-0007766 was identified as a sponge of miR-1233-3p, which could target gene GDF15 to regulate the progression of GC. Finally, hsa-circ-0007766 was evaluated to be a valuable diagnostic marker with a sensitivity of 53.33% and specificity of 83.33% by ROC analysis. This study unveils a mechanism by which hsa-circ-0007766 regulates GDF15 via hsa-circ-0007766/miR-1233-3p/GDF15 axis, which may provide new insight for GC therapeutic strategies.
Keywords: hsa-circ-0007766, miR-1233-3p, GDF15, gastric carcinoma