Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4

Shively, John E.

doi:10.1074/jbc.m115.710160

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Two SNP rs42446897 (75% PPI) and rs42330036 (77% PPI) were identified on BTA 6 at 13.0 and 105.1 Mb, respectively. The SNP rs42446897 was located within an intron in the Calcium/Calmodulin Dependent Protein Kinase II Delta (CAMK2D) gene that has been implicated in various roles associated with heart function (Daniels et al, 2015) and lumen formation of mammary tissue (Nguyen and Shively, 2016). Single nucleotide polymorphism rs42446897 (77% PPI) was located in a non-coding region of the Collapsin Response Mediator Protein 1 (CRMP1) gene whose resulting protein was found expressed in the nervous system of humans.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle

Speidel

Buckley

Boldt

et al. 2018

Journal of Animal Science

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Reproductive performance is the most important component of cattle production from the standpoint of economic sustainability of commercial beef enterprises. Heifer Pregnancy (HPG) and Stayability (STAY) genetic predictions are 2 selection tools published by the Red Angus Association of America (RAAA) to assist with improvements in reproductive performance. Given the importance of HPG and STAY to the profitability of commercial beef enterprises, the objective of this study was to identify QTL associated with both HPG and STAY in Red Angus cattle. A genome-wide association study (GWAS) was performed using deregressed HPG and STAY EBV, calculated using a single-trait animal model and a 3-generation pedigree with data from the Spring 2015 RAAA National Cattle Evaluation. Each individual animal possessed 74,659 SNP genotypes. Individual animals with a deregressed EBV reliability > 0.05 were merged with the genotype file and marker quality control was performed. Criteria for sifting genotypes consisted of removing those markers where any of the following were found: average call rate less than 0.85, minor allele frequency < 0.01, lack of Hardy-Weinberg equilibrium (P < 0.0001), or extreme linkage disequilibrium (r2 > 0.99). These criteria resulted in 2,664 animals with 62,807 SNP available for GWAS. Association studies were performed using a Bayes Cπ model in the BOLT software package. Marker significance was calculated as the posterior probability of inclusion (PPI), or the number of instances a specific marker was sampled divided by the total number of samples retained from the Markov chain Monte Carlo chains. Nine markers, with a PPI ≥ 3% were identified as QTL associated with HPG on BTA 1, 11, 13, 23, and 29. Twelve markers, with a PPI ≥ 75% were identified as QTL associated with STAY on BTA 6, 8, 9, 12, 15, 18, 22, and 23.

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Section: Resultsmentioning

confidence: 99%

Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle

Speidel

Buckley

Boldt

et al. 2018

Journal of Animal Science

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“…Taken together, the fine-tuning of the lumen formation program involves two negative acting signals. One is ID4, a transcription factor that can inhibit other transcription factors (26), and the other is miR-342 that negatively regulates both IRF-1 (38) and DNMT1 (49). The missing upstream regulator not mentioned in the earlier studies is likely CEACAM1.…”

Section: Discussionmentioning

confidence: 98%

“…In support of the second model, overexpression of miR-342 mimics in the lumen-enabled SW cells, abrogates lumen formation. In the accompanying article (49) we show that CEACAM1 can restore ID4 expression by an epigenetic mechanism. Because ID4 may regulate the levels of ID1-3, that in turn, regulate the levels of other transcription factors, the situation could be more complex (44).…”

Section: Discussionmentioning

confidence: 99%

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miRNA-342 Regulates CEACAM1-induced Lumen Formation in a Three-dimensional Model of Mammary Gland Morphogenesis

Weng

Shively

2016

Journal of Biological Chemistry

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Lumen formation of breast epithelium is rapidly lost during tumorigenesis along with expression of cell adhesion molecule CEACAM1. CEACAM1 induces lumena in a three-dimensional culture of MCF7/CEACAM1 cells that otherwise fail to form lumena. We hypothesized miRNAs may be involved because >400 genes were up-or down-regulated in MCF7/CEACAM1 cells and miRNAs may modify global expression patterns. Comparative analysis of miRNA expression in MCF7 versus MCF7/ CEACAM1 cells revealed two miRNAs significantly down-regulated (hsa-miR-30a-3p by 6.73-fold and hsa-miR-342-5p by 5.68-fold). Location of miR-342 within an intron of the EVL gene, hypermethylated and involved in tumorigenesis, suggested that miR-342 overexpression may block lumen formation. In fact, overexpression of miR-342 in MCF7/CEACAM1 cells significantly blocked lumen formation (p < 0.001). ID4, a dominant-negative inhibitor of basic helix-loop-helix transcription factors, up-regulated in MCF7/CEACAM1 cells, down-regulated in breast cancer, and containing a miR-342 binding site, was tested as a potential target of miR-342. The ratio of ID4 to miR-342 increased from 1:2 in MCF7 cells to 30:1 in MCF7/ CEACAM1 cells and a miR-342 inhibitor was able to induce 3-UTR ID4 reporter activity in MCF7 cells. Because 5-methylcytosine methyltransferase DNMT1 is also a potential target of miR-342, we inhibited miR-342 in MCF7 cells and found DNMT1 was up-regulated with no change in EVL expression, suggesting that miR-342 regulates DNMT1 expression but DNMT1 does not affect the EVL expression in these cells. We conclude that the regulation of lumen formation by miR-342 involves at least two of its known targets, namely ID4 and DNMT1.Lumen formation of mammary epithelial cells in a threedimensional culture is an in vitro assay that phenocopies mammary epithelial gland formation (1-3). The loss of lumen formation as exhibited by most, if not all, breast cancer cells in the three-dimensional culture assay phenocopies the premalignant stage of breast cancer know as ductal carcinoma in situ. One approach to identify genes that may govern the change from normal to (pre)malignancy is to transfect breast cancer cells with genes down-regulated in breast cancer and assay their regain of function in the lumen formation assay. A second approach is to block suspect gene expression in breast cancer cells for regain of function, or block gene expression in normal breast epithelial cells for loss of function. One gene that stands out in these assays is the cell-cell adhesion molecule CEACAM1 that is highly expressed in normal breast with a luminal expression pattern (4, 5), and is consistently down-regulated in premalignant and invasive breast cancer (4, 5).Previously, we have shown that transfection of CEACAM1 into MCF7 breast cancer cells resulted in lumen formation when the cells were cultured three-dimensionally (6), whereas anti-CEACAM1 antibodies blocked lumen formation of the normal breast epithelial cell line MCF10F that express CEACAM1 (5). Although CEACAM1 is expressed as mu...

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“…Calcium/calmodulin-dependent protein kinase type II delta (CAMK2D) is a tumor suppressor that mediates the anti-proliferative and differentiating, at least in part through actions of calcium transduction 18 , 19 . Interestingly, recent studies revealed that members of CAMK2 family were implicated in the regulation of epithelial to mesenchymal transition (EMT) process through activation of MAPK and Notch-1 pathways 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-135b/CAMK2D Axis Contribute to Malignant Progression of Gastric Cancer through EMT Process Remodeling

Huangfu¹,

He²,

Han³

et al. 2021

Int. J. Biol. Sci.

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There is a continued need for investigating the roles of microRNAs (miRNAs) and their targets on the progression of gastric cancer (GC), especially metastasis. Here, we performed an integrated study to identify dysregulated miRNAs critical for GC development and progression. miR-135b was determined as a promising biomarker for GC. The expression level of miR-135b was increased among GC cell lines, patient tumor tissues, serum samples, and correlation with aggravation of the GC patients. The in vitro functional assays demonstrated overexpression of miR-135b promoted cell proliferation, migration and invasion in GC, while miR-135b inhibition led to the opposite results. CAMK2D was found to be the direct target of miR-135b, serving as a tumor suppressor in GC cells. Based on our and public datasets, we confirmed the attenuation of CAMK2D expression in GC tissues. And, the expression levels of miR-135b and CAMK2D were closely associated with prognosis of GC patients. Ectopic expression of miR-135b resulted in the down-regulation of CAMK2D. Additionally, CAMK2D was a prerequisite for miR-135b to promote GC cells proliferation and migration by regulating the EMT process, which was confirmed by the in vivo experiments. Importantly, in vivo injection of miR-135b antagomir significantly repressed the tumor growth and metastasis of xenograft models, which suggested that the miR-135b antagomir were promising for clinical applications. Taken together, these results indicate that miR-135b/CAMK2D axis drives GC progression by EMT process remodeling, suggesting that miR-135b may be utilized as a new therapeutic target and prognostic marker for GC patients.

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Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4

Cited by 7 publications

References 47 publications

Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle

Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle

miRNA-342 Regulates CEACAM1-induced Lumen Formation in a Three-dimensional Model of Mammary Gland Morphogenesis

MicroRNA-135b/CAMK2D Axis Contribute to Malignant Progression of Gastric Cancer through EMT Process Remodeling

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