Dataset Information

Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways.

ABSTRACT:

Background

The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored.

Methods

The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/?-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting.

Results

We found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/?-catenin and mTOR signalling pathways.

Conclusions

Circ_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/?-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM.

SUBMITTER: Liu S

PROVIDER: S-EPMC7881613 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways.

Liu Shuting S Chen Liang L Chen Hua H Xu Kangkang K Peng Xi X Zhang Mingchang M

Journal of experimental & clinical cancer research : CR 20210212 1

<h4>Background</h4>The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored.<h4>Methods</h4>The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the ...[more]

PMID: 33579337

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Project description:Breast cancer is the leading cause of cancer-associated deaths among females. In recent decades, microRNAs (miRNAs), a type of short non-coding RNA that regulates gene expression at the post-transcription level, have been reported to participate in the regulation of many hub genes associated with tumorigenesis, tumor progression, and metastasis. However, the precise mechanism by which miRNAs regulate breast cancer metastasis remains poorly discussed, which limits the opportunity for the development of novel, effective therapeutic targets. Here, we aimed to determine the miR-622-related principal regulatory mechanism in cancer. First, we found that miR-622 was significantly related to a poor prognosis in various cancers. By utilizing an integrated miRNA prediction process, we identified 77 promising targets and constructed a protein-protein interaction network. Furthermore, enrichment analyses, including GO and KEGG pathway analyses, were performed to determine the potential function of miR-622, which revealed regulation networks and potential functions of miR-622. Then, we identified a key cluster comprised of six hub genes in the protein-protein interaction network. These genes were further chosen for pan-cancer expression, prognostic and predictive marker analyses based on the TCGA and GEO datasets to mine the potential clinical values of these hub genes. To further validate our bioinformatic results, the regulatory axis of miR-622 and RNF8, one of the hub genes recently reported to promote breast cancer cell EMT process and breast cancer metastasis, was selected as in vitro proof of concept. In vitro, we demonstrated the direct regulation of RNF8 by miR-622 and found that the predicted miR-622-RNF8 axis could regulate RNF8-induced epithelial-mesenchymal transition, cell migration, and cell viability. These results were further demonstrated with rescue experiments. We established a closed-loop miRNA-target-phenotype research model that integrated the bioinformatic analysis of the miRNA target genes and experimental validation of the identified key miRNA-target-phenotype axis. We not only identified the hub target genes of miR-622 in silico but also revealed the regulatory mechanism of miR-622 in breast cancer cell EMT process, viability, and migration in vitro for the first time.

Dataset Information

Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways.

Background

Methods

Results

Conclusions

Publications

Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways.

Similar Datasets

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