Linking short tandem repeat polymorphisms with cytosine modifications in human lymphoblastoid cell lines

Zhou, Zhifeng; Zheng, Yinan; Zhang, Xu; Liu, Cong; Joyce, Brian T.; Kibbe, Warren A.; Hou, Lifang; Zhang, Wei

doi:10.1007/s00439-015-1628-4

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…However, our validation and clinical application tests only focused on the two most common human RE, Alu and LINE-1, due to their predominance throughout the human genome. The algorithm can be used on other human RE such as long terminal repeats and tandem repeats ( 100 ).…”

Section: Discussionmentioning

confidence: 99%

Prediction of genome-wide DNA methylation in repetitive elements

Zheng

Joyce

Liu

et al. 2017

Nucleic Acids Research

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120

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DNA methylation in repetitive elements (RE) suppresses their mobility and maintains genomic stability, and decreases in it are frequently observed in tumor and/or surrogate tissues. Averaging methylation across RE in genome is widely used to quantify global methylation. However, methylation may vary in specific RE and play diverse roles in disease development, thus averaging methylation across RE may lose significant biological information. The ambiguous mapping of short reads by and high cost of current bisulfite sequencing platforms make them impractical for quantifying locus-specific RE methylation. Although microarray-based approaches (particularly Illumina's Infinium methylation arrays) provide cost-effective and robust genome-wide methylation quantification, the number of interrogated CpGs in RE remains limited. We report a random forest-based algorithm (and corresponding R package, REMP) that can accurately predict genome-wide locus-specific RE methylation based on Infinium array profiling data. We validated its prediction performance using alternative sequencing and microarray data. Testing its clinical utility with The Cancer Genome Atlas data demonstrated that our algorithm offers more comprehensively extended locus-specific RE methylation information that can be readily applied to large human studies in a cost-effective manner. Our work has the potential to improve our understanding of the role of global methylation in human diseases, especially cancer.

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Section: Discussionmentioning

confidence: 99%

Prediction of genome-wide DNA methylation in repetitive elements

Zheng

Joyce

Liu

et al. 2017

Nucleic Acids Research

Self Cite

120

View full text Add to dashboard Cite

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Downregulation of PKCζ/Pard3/Pard6b is responsible for lung adenocarcinoma cell EMT and invasion

Zhou

Dai

Chen

et al. 2017

Cellular Signalling

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Atypical protein kinase C ζ (PKCζ) forms an apico-basal polarity complex with Partitioning Defective (Pard) 3 and Pard6 to regulate normal epithelial cell apico-basolateral polarization. The dissociation of the PKCζ/Pard3/Pard6 complex is essential for the disassembly of the tight/adherens junction and epithelial-mesenchymal transition (EMT) that is critical for tumor spreading. Loss of cell polarity and epithelial organization is strongly correlated with malignancy and tumor progression in some other cancer types. However, it is unclear whether the PKCζ/Pard3/Pard6 complex plays a role in the progression of non-small-cell lung cancer (NSCLC). We found that hypoxia downregulated the PKCζ/Pard3/Pard6 complex, correlating with induction of lung cancer cell migration and invasion. Silencing of the PKCζ/Pard3/Pard6 polarity complex components induced lung cancer cell EMT, invasion, and colonization in vivo. Suppression of Pard3 was associated with altered expression of genes regulating wound healing, cell apoptosis/death and cell motility, and particularly upregulation of MAP3K1 and fibronectin which are known to contribute to lung cancer progression. Human lung adenocarcinoma tissues expressed less Pard6b and PKCζ than the adjacent normal tissues and in experimental mouse lung adenocarcinoma, the levels of Pard3 and PKCζ were also decreased. In addition, we showed that a methylation locus in the gene body of Pard3 is positively associated with the expression of Pard3 and that methylation of the Pard3 gene increased cellular sensitivity to carboplatin, a common chemotherapy drug. Suppression of Pard3 increased chemoresistance in lung cancer cells. Together, these results suggest that reduced expression of PKCζ/Pard3/Pard6 contributes to NSCLC EMT, invasion, and chemoresistance.

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Linking short tandem repeat polymorphisms with cytosine modifications in human lymphoblastoid cell lines

Cited by 2 publications

References 60 publications

Prediction of genome-wide DNA methylation in repetitive elements

Prediction of genome-wide DNA methylation in repetitive elements

Downregulation of PKCζ/Pard3/Pard6b is responsible for lung adenocarcinoma cell EMT and invasion

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