CircRNA-NOLC1 mediates Insulin-like growth factor 1 receptor via performing as a ceRNA of miRNA-140-5p to facilitate testicular germ cell tumor advancement.

OBJECTIVE

The study explored the molecular mechanism of circNOLC1 influencing Testicular Germ Cell Tumor (TGCT) progression.

METHODS

The study used TGCT tissue samples and cell lines for investigations. The circNOLC1 and miR-140-5p expression in TGCT tissues were done through RT-qPCR. Analysis of the association of circNOLC1 with TGCT clinic-pathological features was also done. Transfections of circNOLC1, miR-140-5p or Insulin-like GrowthFfactor 1 Receptor (IGF1R)-related sequences or plasmids into TCAM-2 and NCCIT TGCT cells were done. The circNOLC1, miR-140-5p, and IGF1R mRNA expression in cells were done through RT-qPCR. Interaction between miR-140-5p, circNOLC1, and IGF1R was examined using a dual-luciferase reporter assay. MTT assay and colony-forming assay were used to investigate cell proliferation. Apoptosis was determined by flow cytometry. Transwell assay was used to investigate cell invasion. IGF1R protein expression was determined through a western blot.

RESULTS

Increased circNOLC1 in TGCT tissues was correlated with lymph node metastasis, clinical stage, and pathological grade of TGCT patients. CircNOLC1 knock-down inhibited TGCT cell proliferation, colony formation, and invasion, and promotedapoptosis. MiR-140-5p was reduced while IGF1R was upregulated in TGCT tissues and cell lines. Moreover, miR-140-5p mimic could reverse the effect of circNOLC1 knock-down on malignant behaviors of TGCT cells. The authors demonstrated that elevated IGF1R reversed the negative effect of miR-140-5p mimic on TGCT cell proliferation, colony formation, and invasion. CircNOLC1 can act as a sponge of miR-140-5p to up-regulate the IGF1R expression level.

CONCLUSION

The study highlights that circNOLC1 promotes the progression of TGCT by regulating the miR-140-5p/IGF1R axis.