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

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.

SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

“…GSEA indicated that the differential genes grouped according to SLC2A1 expression were primarily participated in REACTOME G ALPHA I SIGNALING EVENTS, REACTOME M PHASE, REACTOME NEURONAL SYSTEM, WP LNCRNA INVOLVEMENT IN CANONICAL WNT SIGNALING AND COLORECTAL CANCER, PID HIF1 TFPATHWAY, and REACTOME GLYCOLYSIS pathways. According to previous research studies, we found that the progression and metastasis of CRC are significantly correlated to the latter three pathways ( Peng et al, 2020 ; Shen et al, 2021 ).…”

A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer

“…NEAT1 has been previously shown to be associated with CRC through several mechanisms of action. NEAT1 is responsible for indirect activation of the Wnt/β‐catenin signaling pathway via binding to DDX5 and KDM5A/Cul4A/Wnt axis 26,82 . In addition, NEAT1 regulates several tumorigenesis‐associated pathways via sponging multiple miRNAs 83 .…”

Long non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) upregulates Cyclin T2 (CCNT2) in laryngeal papilloma through sponging miR-577/miR-1224-5p and blocking cell apoptosis

“…Many studies have revealed critical roles of Lnc-NEAT1 in a variety of cancers. For instance, Fan et al [ 26 ] demonstrated that cancer-related fibroblasts-secreted exosomal Lnc-NEAT1 promoted endometrial cancer development through upregulating miR-26a/b-5p-targeted STAT3 signaling pathway, and Shen et al [ 27 ] testified that lncRNA NEAT1 stimulated malignant behaviors of colorectal cancer through mediating KDM5A/Cul4A and Wnt pathways. Noticeably, consistent with these reports, our findings further validated the oncogenic role of Lnc-NEAT1 in LP.…”