ArticleCarcinogenesis2011
Estrogen-mediated epigenetic repression of the imprinted gene cyclin-dependent kinase inhibitor 1C in breast cancer cells.
Article in Carcinogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Association of breast cancer risk loci with breast cancer survival.International journal of cancer · 2015Pooled it
- Reply to Suresh.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- DNA Methylation of Imprinted GenesCancers · 2022Article
- CDKN1C as a prognostic biomarker correlated with immune infiltrates and therapeutic responses in breast cancer patients.Journal of cellular and molecular medicine · 2021Article
- Article
- The role of CTCF in the organization of the centromeric 11p15 imprinted domain interactome.Nucleic acids research · 2021Article
- Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.Infectious agents and cancer · 2021Article
- Identification of Aberrantly Expressed Long Non-Coding RNAs and Nearby Targeted Genes in Male Osteoporosis.Clinical interventions in aging · 2020Article
- DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions.International journal of cancer · 2018Article
- Long noncoding RNA KCNQ1OT1 promotes proliferation and epithelial‑mesenchymal transition by regulation of SMAD4 expression in lens epithelial cells.Molecular medicine reports · 2018Article
- Gestational oral low-dose estradiol-17β induces altered DNA methylation of CDKN2D and PSAT1 in embryos and adult offspring.Scientific reports · 2018Article
- Overexpression of long non-coding RNA KCNQ1OT1 is related to good prognosis via inhibiting cell proliferation in non-small cell lung cancer.Thoracic cancer · 2018Article
- Reprimo, a Potential p53-Dependent Tumor Suppressor Gene, Is Frequently Hypermethylated in Estrogen Receptor α-Positive Breast Cancer.International journal of molecular sciences · 2017Article
- Long non-coding RNAs and complex diseases: from experimental results to computational models.Briefings in bioinformatics · 2017Review
- Exploration of Deregulated Long Non-Coding RNAs in Association with Hepatocarcinogenesis and Survival.Cancers · 2015Article
- Predicting lncRNA-disease associations and constructing lncRNA functional similarity network based on the information of miRNA.Scientific reports · 2015Article
- Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer.International journal of cancer · 2015Article
- Sex affects bone morphogenetic protein type II receptor signaling in pulmonary artery smooth muscle cells.American journal of respiratory and critical care medicine · 2015Article
- High Skp2/Low p57(Kip2) Expression is Associated with Poor Prognosis in Human Breast Carcinoma.Breast cancer : basic and clinical research · 2015Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
While tumor suppressor genes frequently undergo epigenetic silencing in cancer, how the instructions directing this transcriptional repression are transmitted in cancer cells remain largely unclear. Expression of cyclin-dependent kinase inhibitor 1C (CDKN1C), an imprinted gene on chromosomal band 11 p15.5, is reduced or lost in the majority of breast cancers. Here, we report that CDKN1C is suppressed by estrogen through epigenetic mechanisms involving the chromatin-interacting noncoding RNA KCNQ1OT1 and CCCTC-binding factor (CTCF). Activation of estrogen signaling reduced CDKN1C expression 3-fold (P < 0.001) and established repressive histone modifications at the 5' regulatory region of the locus. These events were concomitant with induction of KCNQ1OT1 expression as well as increased recruitment of CTCF to both the distal KCNQ1OT1 promoter-associated imprinting control region (ICR) and the CDKN1C locus. Transient depletion of CTCF by small interfering RNA increased CDKN1C expression and significantly reduced the estrogen-mediated repression of CDKN1C. Further studies in breast cancer cell lines indicated that the epigenetic silencing of CDKN1C occurs in part as the result of genetic loss of the inactive methylated 11p15.5 ICR allele (R(2) = 0.612, P < 0.001). We also found a novel cis-encoded antisense transcript, CDKN1C-AS, which is induced by estrogen signaling following pharmacologic inhibition of DNA methyltransferase and histone deacetylase activity. Forced expression of CDKN1C-AS was capable of repressing endogenous CDKN1C in vivo. Our findings suggest that in addition to promoter hypermethylation, epigenetic repression of tumor suppressor genes by CTCF and noncoding RNA transcripts could be more common and important than previously understood.
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