ArticleHistology and histopathology2021
Circ_0000376 downregulation inhibits the progression of non-small cell lung cancer by mediating the miR-488-3p/BRD4 axis and the PI3K/PKB signaling pathway.
Article in Histology and histopathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- The IGF2BP3/SLC2A1 axis mediates hsa_circ_0000376-Induced malignant progression and neutrophil N2 polarization in the lung adenocarcinoma microenvironment.Journal of molecular histology · 2026Article
- Metabolic reprogramming and lung cancer focused on roles, mechanism, and clinical prospects of circRNAs: a narrative review.Frontiers in oncology · 2026Review
- Knockdown of circ_0000372 elevates PD-L1 level through sponging miR-488-3p to restrain cell viability, motility and immune escape in gastric cancer.Journal of molecular histology · 2025Article
- Non-coding RNAs and regulation of the PI3K signaling pathway in lung cancer: Recent insights and potential clinical applications.Non-coding RNA research · 2025Review
- Review
- Circ_0000376 regulates miR-577/HK2/LDHA signaling pathway to promote the growth, invasion and glycolysis of osteosarcoma.Journal of orthopaedic surgery and research · 2024Article
- Circular RNA in Non-small Cell Lung Carcinoma: Identification of Targets and New Treatment Modalities.Cancer genomics & proteomics · 2023Review
- The Protective Mechanism of Afuresertib against Esophageal Cancer.Disease markers · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe involvement of circular RNAs (circRNAs) in the development of cancers has attracted much interest. This study aimed to determine the role of circ_0000376 in non-small cell lung cancer (NSCLC) and provide a new mechanism.
methodsThe expression of circ_0000376, miR-488-3p and bromodomain containing 4 (BRD4) mRNA was measured by quantitative real-time PCR (qPCR). Cell behaviors, including cell proliferation, invasion, migration, apoptosis and cell cycle progression were investigated using cell counting kit-8 (CCK-8) assay and colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. The putative relationship between miR-488-3p and circ_0000376 or BRD4 was verified by dual-luciferase reporter assay. The protein levels of BRD4 and phosphorylated PI3K/PKB were detected by western blot. Xenograft model was constructed to determine the role of circ_0000376 in vivo.
resultsCirc_0000376 was highly expressed in NSCLC tissues and cells. Circ_0000376 downregulation inhibited NSCLC cell proliferation, invasion and migration, promoted cell apoptosis and cell cycle arrest and slowed tumor growth in vivo. Circ_0000376 competitively bound to miR-488-3p to regulate the expression of BRD4. Rescue experiments showed that miR-488-3p deficiency reversed the effects of circ_0000376 downregulation, and miR-488-3p restoration-suppressed cell proliferation, migration and invasion were recovered by BRD4 overexpression. Moreover, circ_0000376 downregulation weakened the levels of phosphorylated PI3K and PKB, thus reducing the activity of the PI3K/PKB pathway.
conclusionCirc_0000376 downregulation blocked the development of NSCLC by targeting the miR-488-3p/BRD4 network and suppressing the PI3K/PKB pathway, which broadens knowledge into the understanding of the role of circ_0000376 in NSCLC.
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