Abstract
Earlier studies have shown that circular RNA (circRNA) expression is closely related to the malignant progression of cancer, but the role of circ-DONSON in gastric cancer (GC) has not been fully elucidated. The expression of circ-DONSON, miR-149-5p and lactate dehydrogenase A (LDHA) was measured via qRT-PCR. CCK8 assay was used to assess cell viability, and colony formation assay was performed to detect the number of colonies and the radiosensitivity of cells. Besides, flow cytometry, transwell assay and tube formation assay were employed to determine cell apoptosis, migration, invasion and angiogenesis. Western blot analysis was used to assess the protein expression. The interaction between miR-149-5p and circ-DONSON or LDHA was confirmed by dual-luciferase reporter assay. The influence of circ-DONSON on GC tumor growth in vivo was explored through constructing mice xenograft models. Our results suggested that circ-DONSON was highly expressed in GC tissues and cells. Loss-functional assay results confirmed that silenced circ-DONSON could inhibit the proliferation, metastasis and angiogenesis, while enhance the apoptosis and radiosensitivity of GC cells. In terms of mechanism, circ-DONSON could sponge miR-149-5p, which could target LDHA in GC. MiR-149-5p inhibitor or LDHA overexpression could reverse the suppression effect of circ-DONSON knockdown on GC progression. Additionally, our results also suggested that circ-DONSON silencing could restrain the tumor growth of GC in vivo. These results demonstrated that circ-DONSON could facilitate GC progression by increasing LDHA expression via sponging miR-149-5p, indicating that circ-DONSON might be a novel biomarker for GC treatment.
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10528_2021_10120_MOESM1_ESM.tif
Supplementary file1—Supplementary Fig. 1 The representative images of each experiments for Fig. 3. (A) The representative images for Fig. 3J. (B) The representative images for Fig. 3K. (C) The representative images for Fig. 3L. (D) The representative images for Fig. 3M. (E) The representative images for Fig. 3O. (TIF 12231 kb)
10528_2021_10120_MOESM2_ESM.tif
Supplementary file2—Supplementary Fig. 2 The representative images of each experiments for Fig. 5. (A) The representative images for Fig. 5D. (B) The representative images for Fig. 5E. (C) The representative images for Fig. 5F. (D) The representative images for Fig. 5G. (E) The representative images for Fig. 5I. (TIF 12229 kb)
10528_2021_10120_MOESM3_ESM.tif
Supplementary file3—Supplementary Fig. 3 Selection Candidate miRNA and mRNA. (A-B) AGS and SNU-638 cells were transfected with si-circ-DONSON or circ-DONSON overexpression vector. The expression of 4 candidate miRNAs (miR-330-3p, miR-370-3p, miR-149-5p and miR-638) was assessed using qRT-PCR. (C-D) AGS and SNU-638 cells were transfected with miR-NC or miR-149-5p mimic. The mRNA expression of 4 candidate targets (CDK6, CCND1, SOX4 and LDHA) was detected using qRT-PCR. Data were expressed as mean ± SD from 3 independent experiments, and all independent experiments were set for 3 times to take the average value. *P < 0.05. (TIF 414 kb)
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Shao, Y., Li, F. & Liu, H. Circ-DONSON Facilitates the Malignant Progression of Gastric Cancer Depending on the Regulation of miR-149-5p/LDHA Axis. Biochem Genet 60, 640–655 (2022). https://doi.org/10.1007/s10528-021-10120-4
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DOI: https://doi.org/10.1007/s10528-021-10120-4