Dataset Information

LncRNA GAS5, as a ceRNA, inhibits the proliferation of diffuse large B-cell lymphoma cells by regulating the miR-18a-5p/RUNX1 axis

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a common and fatal malignant tumor caused by B-lymphocytes. Long non-coding RNA (lncRNA) GAS5 (growth arrest specific 5) has been reported to function as a tumor suppressor gene, and is differentially expressed in DLBCL. The present study aimed to explore the potential mechanisms of action of lncRNA GAS5 in the proliferation of DLBCL cells. The expression levels of GAS5, miR-18a-5p and Runt-related transcription factor 1 (RUNX1) in DLBCL cell lines were detected using reverse transcription-quantitative polymerase chain reaction, and their effects on cell proliferation, the cell cycle and apoptosis were determined using 5-ethynyl-2′-deoxyuridine assay and flow cytometry. Dual-luciferase reporter and RNA pull-down assays were used to evaluate the interaction between GAS5 and miR-18a-5p, or between miR-18a-5p and RUNX1. Chromatin immunoprecipitation assay was used to identify the interaction between RUNX1 and BAX. The expression levels of GAS5 and RUNX1 were downregulated; however, miR-18a-5p expression was upregulated in the DLBCL cell lines compared with the normal controls. GAS5 directly interacted with miR-18a-5p by acting as a competing endogenous RNA (ceRNA) and reversed the low expression of RUNX1 induced by miR-18a-5p. Additionally, the knockdown of RUNX1 reversed the inhibitory effects of GAS5 on the proliferation and cell cycle G1 arrest, and its promoting effects on the apoptosis of OCI-Ly3 and TMD8 cells. Moreover, RUNX1 enhanced BAX expression by directly binding to the BAX promoter. On the whole, the present study demonstrates that GAS5 functions as a ceRNA, inhibiting DLBCL cell proliferation by sponging miR-18a-5p to upregulate RUNX1 expression. These findings may provide a potential therapeutic strategy for DLBCL.

SUBMITTER: Miao Y

PROVIDER: S-EPMC8562389 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses a spectrum of diseases, including chronic obstructive bronchitis and emphysema. Pyroptosis is a unique form of inflammatory cell death mediated by the activation of caspase‑1 and inflammasomes. The long non‑coding RNA (lncRNA) growth arrest‑specific 5 (GAS5) is a well‑documented tumor suppressor, which is associated with cell proliferation and death in various diseases. The aim of the present study was to evaluate whether lncRNA GAS5 is associated with the pyroptosis in COPD. To create a COPD cell model, MRC‑5 cells were treated with 10 µg/ml lipopolysaccharide (LPS) for 48 h. Then the level of pro‑caspase 1, caspase 1, IL‑1β, IL‑18, NLRP3 and cleaved gasdermin D (GSDMD) was examined by western blotting. GAS5 mRNA level was detected by qualitative PCR following LPS treatment in MRC‑5 cells. Subsequently, IL‑2, IL‑6, IL‑10 and TNF‑α in MRC‑5 cells was measured by ELISA. Then the proliferation ability of MRC‑5 cells was detected by CCK‑8. Cell death was detected by TUNEL assay. LDH release was measured using an LDH Cytotoxicity Assay kit. The Magna RIP kit was used to validate the interaction between GAS5 and miR‑223‑3p. The present study revealed that increased expression levels of caspase‑1, IL‑1β, IL‑18 and cleaved GSDMD were observed in LPS‑treated MRC‑5 cells, indicating that pyroptosis is involved in COPD progression. Additionally, LPS induced the increase in GAS5 mRNA expression levels and the release of inflammatory factors (IL‑2, IL‑6, IL‑10 and TNF‑α), suggesting that GAS5 is implicated in pyroptosis in COPD. Furthermore, upregulation of GAS5 promoted cell death and inhibited proliferation in the MRC‑5 cell line. Additionally, increased GAS5 expression significantly promoted the production of caspase‑1, IL‑1β, IL‑18, cleaved GSDMD and NLR pyrin domain containing protein 3 (NLRP3). A dual‑luciferase assay demonstrated that GAS5 could directly bind to microRNA‑223‑3p (miR‑223‑3p), and NLRP3 is a direct target of miR‑223‑3p. Furthermore, GAS5 reduced the expression levels of miR‑223‑3p, while it increased the expression levels of NLRP3. The present study concluded that lncRNA GAS5 promoted pyroptosis in COPD by targeting the miR‑223‑3p/NLRP3 axis, implying that GAS5 could be a potential target for COPD.

Dataset Information

LncRNA GAS5, as a ceRNA, inhibits the proliferation of diffuse large B-cell lymphoma cells by regulating the miR-18a-5p/RUNX1 axis

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets