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

Miao,Yinsha; Miao,Yinsha; Miao,Yinsha; Chen,Xiaodong; Chen,Xiaodong; Chen,Xiaodong; Qin,Mengting; Qin,Mengting; Qin,Mengting; Zhou,Wen; Zhou,Wen; Zhou,Wen; Wang,Yang; Wang,Yang; Wang,Yang; Ji,Yanhong; Ji,Yanhong; Ji,Yanhong

doi:10.3892/ijo.2021.5274

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

Authors:
- Yinsha Miao
- Xiaodong Chen
- Mengting Qin
- Wen Zhou
- Yang Wang
- Yanhong Ji
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Affiliations: Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
Published online on: October 22, 2021 https://doi.org/10.3892/ijo.2021.5274
Article Number: 94
Copyright: © Miao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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