Dataset Information

MiR-340 Promotes Retinoblastoma Cell Proliferation, Migration and Invasion Through Targeting WIF1.

ABSTRACT:

Background

MicroRNAs (miRNAs) function as important regulators of gene expression involved in tumor pathogenesis, including retinoblastoma. However, the expression profiles and potential roles in retinoblastoma are still largely unclear.

Material and methods

Differentially expressed miRNAs (DEmiRs) and genes (DEGs) in retinoblastoma were extracted from Gene Expression Omnibus (GEO) repository. Expression levels of miR-340 and WIF1 were detected in retinoblastoma tissues and cell lines by qRT-PCR. Both gain-of-function and loss-of-function experiments were performed to explore the effects of miR-340 on cell proliferation, migration and invasion. Bioinformatics analysis and luciferase reporter assay were used to explore the interaction between miR-340 and WIF1.

Results

A total of 11 DEmiRs were identified in retinoblastoma tissue and blood samples. Among them, we validated that miR-340 was the most highly expressed miRNA and correlated with tumor size, ICRB stage and optic nerve invasion. miR-340 was observed to enhance the proliferation, migration and invasion capacity of retinoblastoma cells. We then identified 26 DEGs from 3 retinoblastoma GEO datasets and subsequently constructed a miRNA-mRNA regulatory network. Further analysis revealed that WIF1 was a direct target of miR-340. Moreover, overexpression of WIF1 could repress retinoblastoma progression induced by miR-340 in vitro and in vivo.

Conclusion

Collectively, miR-340 functioned as an oncomiRNA to promote retinoblastoma cell proliferation, migration and invasion via regulating WIF1. Our data also provided multiple miRNAs and genes that may contribute to a better understanding of retinoblastoma pathogenesis.

SUBMITTER: Li K

PROVIDER: S-EPMC8187089 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The authors' previous study revealed that the serum levels of microRNA (miR)-663b are significantly increased in patients with nasopharyngeal carcinoma (NPC), and are associated with NPC progression and poor prognosis. However, the molecular mechanism of underlying NPC growth and metastasis remains unclear. In the present study, quantitative polymerase chain reaction and western blot analyses were performed to examine changes to mRNA and protein expression, respectively. MTT, wound healing and Transwell assays were used to examine cell proliferation, migration and invasion, respectively. Luciferase reporter gene assays were performed to identify target genes of miR-663b. It was demonstrated that miR-663b was significantly upregulated in NPC tissue compared with non-tumor nasopharyngeal epithelial tissue samples. Furthermore, miR-663b expression gradually increased with advancing stages of NPC, with the highest expression being observed in the latest stage IV. The increased expression of miR-663b was associated with advanced clinical stage and lymph node metastasis. In addition, miR-663b expression was increased in NPC cell lines compared with normal nasopharyngeal epithelial NP69 cells. Knockdown of miR-663b resulted in a significant reduction in the proliferation, migration and invasion of NPC CNE1 cells. Tumor suppressor candidate 2 (TUSC2) was identified as a novel target gene of miR-663b. It was further demonstrated that TUSC2 was significantly downregulated in NPC tissue samples and cell lines. miR-663b negatively regulated the expression of TUSC2 at the post-transcriptional level in CNE1 cells. Additionally, inhibition of TUSC2 expression attenuated the suppressive effects of miR-663b downregulation on the proliferation, migration and invasion of CNE1 cells. To the best of our knowledge, this is the first study to demonstrate that miR-663b, which is upregulated in NPC, promotes the proliferation, migration and invasion of NPC cells, partially through the inhibition of TUSC2 expression. Therefore, it is suggested that miR-663b is a promising therapeutic target for the treatment of patients with NPC.