ArticleAmerican journal of translational research2022
DNMT3b-mediated SPAG6 promoter hypermethylation affects lung squamous cell carcinoma development through the JAK/STAT pathway.
Article in American journal of translational research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Role of SPAG6 in regulating physiological functions and tumorigenesis (Review).International journal of oncology · 2026Review
- DNMT3b promotes proliferation and invasion by mediating HOPX DNA methylation in lung cancer.iScience · 2026Article
- CircMYH9 promotes the mRNA stability of SPAG6 by recruiting EIF4A3 to facilitate the progression of breast cancer.Epigenetics · 2025Article
- SPAG6 Promotes Multiple Myeloma Through Activation of the MAPK/ERK Signaling Pathway.Frontiers in pharmacology · 2025Article
- Epigenetic crosstalk between stem cells and tumors: mechanisms and emerging perspectives.American journal of stem cells · 2025Review
- Post-translational modifications of protein and lung cancer.Frontiers in oncology · 2025Review
- Article
- CARF regulates the alternative splicing and piwi/piRNA complexes during mouse spermatogenesis through PABPC1.Acta biochimica et biophysica Sinica · 2024Article
- Review
- A comprehensive pan-cancer analysis revealingGland surgery · 2024Article
- SPAG6 overexpression decreases the pro-apoptotic effect of daunorubicin in acute myeloid leukemia cells through the ROS/JNK MAPK axis in a GSTP1-dependent manner.Frontiers in pharmacology · 2024Article
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA methylation controls the transcription of genes and is involved in the development of lung cancer. Our preliminary bioinformatics prediction revealed that sperm associated antigen 6 (SPAG6) was considerably hypermethylated in lung squamous cell carcinoma (LUSC). Thus, this study aimed to probe the mechanism underlying its hypermethylation.
methodsThe effect of DNA methylation of SPAG6 on its expression in LUSC was analyzed. The contributors to SPAG6 DNA hypermethylation were sought. CCK-8, EdU, and Transwell assays were carried out to assess the malignant phenotype of LUSC cells. KEGG pathway enrichment analysis was used to screen for pathways affected by SPAG6, which were confirmed by dual-luciferase assays. Bioinformatics analysis was conducted to dissect the impact of SPAG6 on the immune response and cancer cell stemness in LUSC.
resultsDNA methyltransferase 3b (DNMT3b)-mediated hypermethylation of the SPAG6 promoter in LUSC led to SPAG6 downregulation. SPAG6 reverted the malignant phenotype of LUSC cells. SPAG6 regulated the JAK/STAT pathway by inhibiting the transcription of STAT1 and STAT3. The expression of SPAG6 was positively related to immune infiltration in LUSC and inversely related to the expressions of the immunosuppressive genes CTLA4 and PDCD1. SPAG6 expression was negatively correlated with cancer cell stemness in LUSC, and its expression inhibited the expressions of Nanog, ALDH1, and Sox2, markers of cancer cell stemness.
conclusionsDNMT3b-mediated SPAG6 promoter hypermethylation activates the JAK/STAT pathway to promote LUSC progression.
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Identifiers
36398260PMC9641444W4309408900What OpenQuestion holds
Registered trials
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