Dataset Information

MiRNA-425-5p enhances diffuse large B cell lymphoma growth by targeting PTEN

ABSTRACT:

Background

At present, cancer is one of the greatest threats to mankind, and is associated with the highest rates of morbidity and comorbidity. Recently, the advancements in molecular biology have led to an in-depth understanding of the underlying pathophysiology, which may further impact the lead time in the context of early discovery and effective therapy of cancer. Therefore, the present study proposes a better understanding of the role of micro(miR)-425-5p in diffuse large B-cell lymphoma (DLBC).

Methods

qRT-PCR was carried out to detect the relevant proteins, miRNA and mRNA RNA gene expression in DLBC cells. The effect of miR-425-5p on DLBC growth was examined by CCK-8 and colony formation assays. The binding relationship between genes was verified by dual-luciferase reporter gene assay.

Results

We demonstrated how the over-expression of miR-425-5p can lead to increased progression of DLBC by increasing the cellular proliferation rate and colony-forming ability. Additionally, we also found that the expression of miR-425-5p could be significantly inhibited on the basis of phosphatase and tensin homolog (PTEN) signaling pathways.

Conclusions

The present study concludes that miR-425-5p is responsible for the oncogenic progression and relapse of DLBC tumorigenesis via PTEN/PI3K signaling, which can thus be effectively used to achieve better therapeutic outcomes.

SUBMITTER: Wu W

PROVIDER: S-EPMC8799000 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundCD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions.MethodsWeighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models.ResultsMiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation.ConclusionsMiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.