ArticleCancer research and treatment2023
MLL4 Regulates the Progression of Non-Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis.
Article in Cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions.International journal of molecular sciences · 2025Article
- A positive feedback loop of OTUD1 and c-Jun driven by leptin expedites stemness maintenance in ovarian cancer.Oncogene · 2025Article
- UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway.Journal of cancer research and clinical oncology · 2024Article
- Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling.Regenerative therapy · 2024Article
- Landscape of targeted therapies for lung squamous cell carcinoma.Frontiers in oncology · 2024Review
- Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.Frontiers in oncology · 2024Review
- KMT2D Induces M1 Macrophage Polarization to Repress Non-small Cell Lung Cancer Progression via Transcription Activation of ITGAL.Iranian journal of pharmaceutical research : IJPRArticle
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
purposeMixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. Materials and Methods: RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
resultsWe found that MLL4 expression was downregulated in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
conclusionOur findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.
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