lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway

Shen,Xudong; Ye,Zhenyu; Wu,Wei; Zhao,Kui; Cheng,Guilian; Xu,Liming; Gan,Lei; Wu,Yongyou; Yang,Zhixue

doi:10.3892/ijo.2021.5231

lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway

Authors:
- Xudong Shen
- Zhenyu Ye
- Wei Wu
- Kui Zhao
- Guilian Cheng
- Liming Xu
- Lei Gan
- Yongyou Wu
- Zhixue Yang
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Affiliations: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
Published online on: June 8, 2021 https://doi.org/10.3892/ijo.2021.5231
Article Number: 51

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Abstract

Colorectal cancer (CRC) is a major cause of cancer‑related mortality. The aberrant expression of long non‑coding RNAs (lncRNAs) is implicated in the pathogenesis of CRC. The present study investigated the role of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in CRC. lncRNA NEAT1 expression was detected in CRC tissues and cell lines. HCT116 cells were transfected with si‑NEAT1, and the malignant behavior of the cells was detected. The binding associations between NEAT1 and E2F1, as well as between E2F1 and KDM5A were verified. si‑NEAT1‑transfected cells were also transfected with si‑KDM5A. H3K4me3 methylation and cullin 4A (Cul4A) expression in HCT116 cells were detected. The si‑NEAT1‑transfected cells were also transfected with pc‑Cul4A. Proteins related to the Wnt pathway were detected. A xenograft model of CRC using nude mice was established and the mice were injected with si‑NEAT1‑transfected HCT116 cells. lncRNA NEAT1 was found to be upregulated in CRC tissues and cells. NEAT1 silencing inhibited the malignant behaviors of the HCT116 cells. lncRNA NEAT1 inhibited KDM5A expression by binding to E2F1. The downregulation of KDM5A reversed the inhibitory effects of NEAT1 silencing on the malignant behavior of the cells. KDM5A inhibited Cul4A expression via the demethylation of H3K4me3. The overexpression of Cul4A promoted the malignant behavior of the si‑NEAT1‑transfected HCT116 cells. lncRNA NEAT1 activated the Wnt pathway via KDM5A/Cul4A. In vivo experiments confirmed the role of NEAT1 in CRC. On the whole, the present study demonstrates that lncRNA NEAT1 facilitates the progression of CRC via the KDM5A/Cul4A/Wnt axis.

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