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Retroelements: molecular features and implications for disease.
Jung, Yi-Deun,Ahn, Kung,Kim, Yun-Ji,Bae, Jin-Han,Lee, Ja-Rang,Kim, Heui-Soo Genetics Society of Japan 2013 Genes & genetic systems Vol.88 No.1
<P>Eukaryotic genomes comprise numerous retroelements that have a major impact on the structure and regulation of gene function. Retroelements are regulated by epigenetic controls, and they generate multiple miRNAs that are involved in the induction and progression of genomic instability. Elucidation of the biological roles of retroelements deserves continuous investigation to better understand their evolutionary features and implications for disease.</P>
Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells.
Jung, Yi-Deun,Shim, Jae-Woong,Park, Seong-Joon,Choi, Si Ho,Yang, Kwangmo,Heo, Kyu,Park, Moon-Taek Lychnia 2015 International journal of oncology Vol.46 No.3
<P>Activation of epithelial-mesenchymal transition (EMT) is important for malignant tumor progression exhibiting migratory and invasive properties. UHRF1 (ubiquitin-like, with PHD and RING finger domains 1), as an epigenetic regulator, plays a crucial role in DNA CpG methylation, chromatin remodeling and gene expression. Many studies demonstrated that UHRF1 is aberrantly expressed in various types of human cancer. However, the precise role of UHRF1 in human cancers remains highly controversial. In the present study, we found that downregulation of UHRF1 enhances the migratory and invasive properties of human cancer cells by inducing EMT, and that the CXCR4 signaling pathway is strictly necessary for UHRF1 deficiency-mediated induction of EMT. Downregulation of UHRF1 induced the expression of the EMT-regulating transcription factors, Zeb1, Slug and Snail and then led to decreased protein level of E-cadherin, and increased protein level of N-cadherin and vimentin, including increased migratory and invasive properties of human cancer cells. In addition, siRNA targeting of Zeb1 or Snail effectively attenuated UHRF1 deficiency-induced EMT, but siRNA targeting of Slug did not, indicating that Zeb1 and Snail play key roles in this event. Moreover, downregulation of UHRF1 induced the expression of CXCR4 in HepG2 cells. siRNA targeting of CXCR4 greatly suppressed the UHRF1 deficiency-induced EMT, as evidenced by a reversal of expression patterns of Snail and Zeb1, and by reduced migratory and invasive properties of HepG2 cells. In conclusion, our results demonstrate that downregulation of UHRF1 contributes to the induction of EMT in human cancer cells via the activation of CXCR4 signaling pathway. Our observation also suggests that UHRF1 may play a pivotal role in suppressing the malignant alteration of cancer cells.</P>
No expression of porcine endogenous retrovirus after pig to monkey xenotransplantation
Seongsoo Hwang,Yi-Deun Jung,Kahee Cho,Sun-A Ock,Keon-Bong Oh,Heui-Soo Kim,Ik-Jin Yun,Curie Ahn,Jin-Ki Park,Seoki Im 한국실험동물학회 2014 Laboratory Animal Research Vol.30 No.2
This study was performed to investigate the expression of two porcine endogenous retrovirus (PERV) elements, PERV gag and full-length conserved PERV, in blood cells collected periodically from organrecipient monkeys that underwent pig to non-human primate xenotransplantation. The heart and kidney—respectively acquired from α-1,3-galactosyltransferase knockout (GT-KO) pigs that survived for24 and 25 days—were xenografted into cynomolgus monkeys. The two PERV elements expressed in the xenografted GT-KO pig organs were not present in the blood cells of the recipient monkeys. In the present study, we deduced that PERVs are not transmitted during GT-KO pig to monkey xenotransplantation.
Park, Sang-Je,Huh, Jae-Won,Kim, Dae-Soo,Ha, Hong-Seok,Jung, Yi-Deun,Ahn, Kung,Oh, Keon-Bong,Park, Eung-Woo,Chang, Kyu-Tae,Kim, Heui-Soo Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.4
The pig genome contains the gamma1 family of porcine endogenous retroviruses (PERVs), which are major obstacle to the development of successful xenotransplantation from pig to human. Long terminal repeats (LTRs) found in PERVs are known to be essential elements for the control of the transcriptional activity of single virus by different transcription factors (TFs). To identify transcribed PERV LTR elements, RT-PCR and DNA sequencing analyses were performed. Twenty-nine actively transcribed LTR elements were identified in the kidney tissues of the NIH-Miniature pig. These elements were divided into two major groups (I and II), and four minor groups (I-1, I-2, I-3, and II-1), by the presence of insertion and deletion (INDEL) sequences. Group I elements showed strong transcriptional activity compared to group II elements. Four different LTR elements (PL1, PL2, PL3, and PL4) as representative of the groups were analyzed by using a transient transfection assay. The regulation of their promoter activity was investigated by treatment with M.SssI (CpG DNA methyltransferase) and garcinol (histone acetyltransferase inhibitor). The transcriptional activity of PERV LTR elements was significantly reduced by treatment with M.SssI. These data indicate that transcribed PERV LTR elements harbor sufficient promoter activity to regulate the transcription of a single virus, and the transcriptional activity of PERV LTRs may be controlled by DNA methylation events.