# 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

## TL;DR

This study shows that circRNA-NOLC1 helps testicular germ cell tumors grow by blocking a specific microRNA, which in turn boosts a cancer-promoting protein.

## Contribution

The study reveals a novel regulatory mechanism involving circNOLC1, miR-140–5p, and IGF1R in testicular germ cell tumor progression.

## Key findings

- CircNOLC1 acts as a sponge for miR-140–5p, increasing IGF1R expression in testicular germ cell tumors.
- Reducing circNOLC1 or increasing miR-140–5p inhibits tumor cell growth and invasion.
- Elevated circNOLC1 is linked to worse tumor characteristics like lymph node metastasis and higher clinical stage.

## Abstract

•CircNOLC1 and IGF1R are upregulated while miR-140–5p is downregulated in TGCT.•CircNOLC1 can act as a sponge of miR-140–5p to up-regulate IGF1R.•Silencing circNOLC1 or overexpressing miR-140–5p inhibits TGCT cell proliferation, colony formation, and invasion, and promotes cell apoptosis.•CircNOLC1 promotes the progression of TGCT by modulating the miR-140–5p/IGF1R axis.

CircNOLC1 and IGF1R are upregulated while miR-140–5p is downregulated in TGCT.

CircNOLC1 can act as a sponge of miR-140–5p to up-regulate IGF1R.

Silencing circNOLC1 or overexpressing miR-140–5p inhibits TGCT cell proliferation, colony formation, and invasion, and promotes cell apoptosis.

CircNOLC1 promotes the progression of TGCT by modulating the miR-140–5p/IGF1R axis.

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

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.

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.

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