ArticlePloS one2013
Down-regulation of SIX3 is associated with clinical outcome in lung adenocarcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- The expression profile and clinic significance of the SIX family in non-small cell lung cancer.Journal of hematology & oncology · 2016Pooled it
- Pooled it
- Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals.Clinical epigenetics · 2018Trial
- Review
- SIX3 as a Regulator of Development and Disease.Journal of developmental biology · 2026Review
- KDM5C-regulated SIX5 promotes glioblastoma progression through transcriptional activation of UBE2C and enhancement of the Warburg effect.Frontiers in immunology · 2026Article
- Retinal determination gene networks: from biological functions to therapeutic strategies.Biomarker research · 2023Review
- Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.Human molecular genetics · 2023Article
- SIX3 function in cancer: progression and comprehensive analysis.Cancer gene therapy · 2022Review
- Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer.Cell death discovery · 2021Article
- The SIX Family of Transcription Factors: Common Themes Integrating Developmental and Cancer Biology.Frontiers in cell and developmental biology · 2021Review
- Article
- TNFRSF12A and a new prognostic model identified from methylation combined with expression profiles to predict overall survival in hepatocellular carcinoma.Translational cancer research · 2020Article
- SIX3 and SIX6 interact with GEMININ via C-terminal regions.Biochemistry and biophysics reports · 2019Article
- SNPs in LncRNA genes are associated with non-small cell lung cancer in a Chinese population.Journal of clinical laboratory analysis · 2019Article
- A novel long noncoding RNA lncWDR26 suppresses the growth and metastasis of hepatocellular carcinoma cells through interaction with SIX3.American journal of cancer research · 2018Article
- The Homeotic Protein SIX3 Suppresses Carcinogenesis and Metastasis through Recruiting the LSD1/NuRD(MTA3) Complex.Theranostics · 2018Article
- Epigenetically controlled Six3 expression regulates glioblastoma cell proliferation and invasion alongside modulating the activation levels of WNT pathway members.Journal of neuro-oncology · 2017Article
- SIX3, a tumor suppressor, inhibits astrocytoma tumorigenesis by transcriptional repression of AURKA/B.Journal of hematology & oncology · 2017Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundLung cancer is a common cancer and the leading cause of cancer-related death worldwide. SIX3 is a human homologue of the highly conserved sine oculis gene family essential during embryonic development in vertebrates, and encodes a homeo-domain containing transcription factor. Little is known about the role of SIX3 in human tumorigenesis. This study is to assess the expression/function of SIX3 and the significance of SIX3 as a prognostic biomarker in lung adenocarcinoma.
methodsQuantitative real-time RT-PCR was used to analyze SIX3 mRNA expression and quantitative methylation specific PCR (MSP) was used to examine promoter methylation. MTS and colony formation assays were performed to examine cell proliferation. Wound healing assays were used to assess cell migration, and microarrays were utilized to examine genes regulated by SIX3 in lung cancer cells. Association of SIX3 expression levels with clinical outcomes of patients with lung adenocarcinoma was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model.
resultsSIX3 was down-regulated in lung adenocarcinoma tissues compared to their matched adjacent normal tissues, and this down-regulation was associated with methylation of the SIX3 promoter. SIX3 was also methylation-silenced in lung cancer cell lines. Restoration of SIX3 in lung cancer cells lacking endogenous SIX3 suppressed cell proliferation and migration, and downregulated a number of genes involved in proliferation and metastasis such as S100P, TGFB3, GINS3 and BAG1. Moreover, SIX3 mRNA expression was associated with significantly improved overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients and patients with bronchioloalveolar carcinoma (BAC) features.
conclusionsSIX3 may play an important role as a novel suppressor in human lung cancer. SIX3 has potential as a novel prognostic biomarker for patients with lung adenocarcinomas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.