Paternally Expressed Gene 10 Expression Research Articles

Targeting PEG10 as a novel therapeutic approach to overcome CDK4/6 inhibitor resistance in breast cancer

BackgroundBreast cancer is the global leading cancer burden in women and the hormone receptor-positive (HR+) subtype is a major part of breast cancer. Though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are highly effective therapy for HR+ subtype, acquired resistance is inevitable in most cases. Herein, we investigated the paternally expressed gene 10 (PEG10)-associated mechanism of acquired resistance to CDK4/6 inhibitors.MethodsPalbociclib-resistant cells were generated by exposing human HR+ breast cancer cell lines to palbociclib for 7–9 months. In vitro mechanistic study and in vivo xenograft assay were performed. For clinical relevance, public mRNA microarray data sets of early breast cancer were analyzed and PEG10 immunohistochemical staining was performed using pre-CDK4/6 inhibitor tumor samples.ResultsWe observed that PEG10 was significantly upregulated in palbociclib-resistant cells. Ectopic overexpression of PEG10 in parental cells caused CDK4/6 inhibitor resistance and enhanced epithelial–mesenchymal transition (EMT). On the contrary, PEG10-targeting siRNA or antisense oligonucleotides (ASOs) combined with palbociclib synergistically inhibited proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice and suppressed EMT as well. The mechanistic study confirmed that high PEG10 expression suppressed p21, a natural CDK inhibitor, and SIAH1, a post-translational degrader of ZEB1, augmenting CDK4/6 inhibitor resistance. Then PEG10 siRNA combined with palbociclib suppressed cell cycle progression and EMT via activating p21 and SIAH1, respectively. Consequently, combined PEG10 inhibition and palbociclib overcame CDK4/6 inhibitor resistance. Furthermore, high PEG10 expression was significantly associated with a shorter recurrence-free survival (RFS) based on public mRNA expression data. In pre-CDK4/6 inhibitor treatment tissues, PEG10 positivity by IHC also showed a trend toward a shorter progression-free survival (PFS) with CDK4/6 inhibitor. These results support clinical relevance of PEG10 as a therapeutic target.ConclusionsWe demonstrated a novel PEG10-associated mechanism of CDK4/6 inhibitor resistance. We propose PEG10 as a promising therapeutic target for overcoming PEG10-associated resistance to CDK4/6 inhibitors.

Folate deficiency disturbs PEG10 methylation modifications in human spina bifida.

Paternally expressed gene 10 (PEG10) is believed to be a key imprinted gene involved in placenta formation. However, its role in human folate-related spina bifida (SB) remains unclear. The methylation status of the germline differentially methylated region (gDMR) in the PEG10/sarcoglycan epsilon (SGCE) imprinted cluster was compared between SB patients and control samples. Moreover, the influence of ectopic PEG10 expression on apoptosis was assessed to explore the underlying mechanisms related to folate deficiency-induced aberrant gDMR methylation in SB. The case group exhibited a significant increase in the methylation level of the gDMR and a marked reduction in the mRNA and protein expression of PEG10 compared with the control group. A prominent negative correlation was found between the folate level in brain tissue and gDMR methylation status (r = -0.62, P = 0.001). A cell model treated with a demethylating agent showed a significant elevation of PEG10 transcription level, as well as other imprinted genes in this cluster. In addition, the inhibition of PEG10 was found to be accompanied by aberrant activation of apoptosis in SB. Our findings suggest that disturbed gDMR methylation of the PEG10/SGCE cluster due to folate deficiency is involved in SB through aberrant activation of apoptosis. Disturbed genomic imprinting has been verified to be involved in neural tube defects (NTDs). However, little is known about the effect of ectopic expression of imprinted gene PEG10 on human NTDs. Aberrant methylation status of the germline differentially methylated region (gDMR) of PEG10/SGCE cluster due to folate deficiency has been found to result in the inhibition of PEG10 and has a marked association with an increased occurrence of spina bifida. Inhibited expression of PEG10 partly is found to be related to the abnormal activation of apoptosis in spina bifida.

PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma

AbstractMycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, undergo large-cell transformation (LCT) in the late stage, manifesting aggressive behavior, resistance to treatments, and poor prognosis, but the mechanisms involved remain unclear. To identify the molecular driver of LCT, we collected tumor samples from 133 MF patients and performed whole-transcriptome sequencing on 49 advanced-stage MF patients, followed by integrated copy number inference and genomic hybridization. Tumors with LCT showed unique transcriptional programs and enriched expressions of genes at chr7q. Paternally expressed gene 10 (PEG10), an imprinted gene at 7q21.3, was ectopically expressed in malignant T cells from LCT, driven by 7q21.3 amplification. Mechanistically, aberrant PEG10 expression increased cell size, promoted cell proliferation, and conferred treatment resistance by a PEG10/KLF2/NF-κB axis in in vitro and in vivo models. Pharmacologically targeting PEG10 reversed the phenotypes of proliferation and treatment resistance in LCT. Our findings reveal new molecular mechanisms underlying LCT and suggest that PEG10 inhibition may serve as a promising therapeutic approach in late-stage aggressive T-cell lymphoma.

Influence of conception and delivery mode on stress response marker Oct4B1 and imprinted gene expression related to embryo development: A cohort study.

BackgroundRecent scientific data support that the mode of conception and delivery may influence epigenetic regulation and therefore embryo development. Octamer-binding transcription factor 4-B1 (OCT4B1), a novel variant of OCT4 with yet unknown biological function, is suggested to have a potential role in mediating cellular stress response. Furthermore, Insulinlike Growth Factor 2 (IGF2), Mesoderm-specific Transcript (MEST) and paternally expressed gene 10 (PEG10) are genes known as imprinted and are regulated via means of epigenetic regulation. The influence of delivery mode and conception on epigenetic regulation is an active research field.ObjectiveOur aim was to correlate the expression level of Oct4B1 and the expression and methylation level of IGF2, MEST, and PEG10 imprinted genes with the mode of delivery and conception in the umbilical cord blood of newborns.Materials and MethodsSamples of umbilical cord blood from infants born after vaginal delivery, caesarean section (CS) with the infant in cephalic position and CS due to breech position were examined. Furthermore, the investigation included infants conceived through means of assisted reproductive technology.ResultsNo statistically significant differences were found in mRNA expression levels between different modes of conception and delivery (p = 0.96). Oct4B1, IGF2, MEST, and PEG10 expression levels do not seem to be significantly affected by different modes of conception and delivery.ConclusionThese results indicate that the expression and methylation patterns of Oct4B1, IGF2, MEST and PEG10 in umbilical cord blood are not affected by the conception and delivery mode.

Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion, and Survival of Bladder Cancer.

Paternally expressed gene 10 (PEG10) has been associated with neuroendocrine muscle-invasive bladder cancer (MIBC), a subtype of the disease with the poorest survival. In this work, we further characterized the expression pattern of PEG10 in The Cancer Genome Atlas database of 412 patients with MIBC, and found that, compared with other subtypes, PEG10 mRNA level was enhanced in neuroendocrine-like MIBC and highly correlated with other neuroendocrine markers. PEG10 protein level also associated with neuroendocrine markers in a tissue microarray of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared with parental cells, and knocking down of PEG10 resensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell-cycle regulators p21 and p27 and delayed G1-S-phase transition, while overexpression of PEG10 enhanced cancer cell proliferation. PEG10 silencing also lowered levels of SLUG and SNAIL, leading to reduced invasion and migration. In an orthotopic bladder cancer model, systemic treatment with PEG10 antisense oligonucleotide delayed progression of T24 xenografts. In summary, elevated expression of PEG10 in MIBC may contribute to the disease progression by promoting survival, proliferation, and metastasis. Targeting PEG10 is a novel potential therapeutic approach for a subset of bladder cancers.

PEG10 counteracts signaling pathways of TGF-β and BMP to regulate growth, motility and invasion of SW1353 chondrosarcoma cells.

Recently, we reported highly active transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-β signaling, and PEG10 interfered with the TGF-β and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-β1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-β1-induced motility of SW1353 cells. Individually, TGF-β1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-β signaling and inhibiting cell motility and invasion by interfering with TGF-β and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.

Prognostic value of PEG10 in Asian solid tumors: A meta-analysis

BackgroundThe involvement of paternally expressed gene 10 (PEG10) in the development of solid tumors has been demonstrated. However, the available data have not yet been fully analyzed. We conducted this meta-analysis to evaluate the correlations between PEG10 and the clinicopathological characteristics in patients with solid tumors. MethodsAn electronic search for relevant articles was conducted in PubMed, Web of Science, Cochrane Library, EMBASE, Chinese CNKI, and Wan Fang. The relationships between PEG10 and the clinicopathological features and prognosis of patients with cancer were determined using pooled odds ratios and hazard ratios with 95% confidence interval (CI). ResultsTen studies comprising 1014 patients were included. The pooled analyses indicated the significant association of PEG10 overexpression with the risk of cancer, differentiation, lymph node metastasis and advanced TNM stage, but not with gender in cancer patients. Moreover, a high level of PEG10 expression correlated with poor prognosis and could be used as an independent prognostic biomarker for patients with solid tumors. ConclusionsPEG10 expression is associated with advanced clinicopathological characteristics and can be used as a prognostic biomarker in patients with solid tumors.

The effects of Curcumin on HCT-116 cells proliferation and apoptosis via the miR-491/PEG10 pathway.

Paternally expressed gene-10 (PEG10) could participate in several carcinomas and might be regulated by miR-491. To now, miR-491 was found to play an important role in the sensitivity and mechanism of drug usage in the treatment of colorectal cancer, and drug resistance is a key factor to affect the disease healing. In this study, miR-491, PEG10, Wnt1, and β-catenin expression levels and their correlation with colorectal cancer were assessed in cancer tissues and adjacent parts. And the target relationship between PEG10 and miR-491 was verified. Meanwhile, the impaction of Curcumin on miR-491, PEG10, and Wnt/β-catenin signaling pathway were analyzed in HCT-116 cells. The effects of PEG10 and Curcumin on human HCT-116 cells proliferation and apoptosis were investigated by MTT and flow cytometry assay. Results showed that the expression of miR-491 in colon cancer tissues was decreased, but PEG10, Wnt1, and β-catenin were higher than that in adjacent tissues. The PEG10 gene 3' UTR could combine with miR-491 seed sequence and miR-491 overexpression could cause a decrease in PEG10, Wnt1, and β-catenin levels in human HCT-116 cells. Furthermore, PEG10 overexpression increased the expression levels of Wnt1 and β-catenin, thereby promoting cell proliferation and inhibiting apoptosis. In addition, Curcumin could up-regulate miR-491, inhibit PEG10, and Wnt/β-catenin signaling pathway. Consequently, Curcumin reduced HCT-116 cells proliferation and promoted cells apoptosis via the miR-491/PEG10 pathway. In conclusion, PEG10 was a target gene of miR-491, miR-491/PEG10 strengthen the sensitivity of Curcumin in HCT-116 cells proliferation and apoptosis, which might act as an ideal diagnostic biomarker treatment methods.

Knockdown of long non-coding RNA PEG10 inhibits growth, migration and invasion of gastric carcinoma cells by up-regulating miR-3200

Gastric cancer is the main leading cause of cancer-related death worldwide. The aberrant expression of paternally expressed gene 10 (PEG10) is involved in development of a range of cancers. However, the potential biological function and the underling mechanism of PEG10 in human gastric carcinoma are still unknown. Knocking down LncRNA PEG10 might represent a promising therapeutic strategy for the treatment of gastric cancer. The expression of PEG10, miR-3200, and AEG1 in human gastric carcinoma NCI-N87 cells were altered by cell transfection assay. Cell viability, migration, invasion, and apoptosis were determined by trypan blue exclusion, Transwell assay, and flow cytometric analysis, respectively. RNA and protein expression level of gene was analyzed by real-time PCR and Western blot. Luciferase reporter assay was conducted to determine the target gene of miR-3200. JNK and Wnt signal pathway protein expressions were tested by Western blot. The up-regulation of PEG10 was found in clinical samples. PEG10 knockdown effectively inhibited gastric carcinoma cell viability, migration, and invasion, but promoted cell apoptosis. This tumor-suppressing effect of PEG10 knockdown might be realized by up-regulating miR-3200 in vitro and in vivo. AEG1 was a direct target gene of miR-3200. Moreover, miR-3200 might suppress NCI-N87 cells by negative regulating AEG1. Up-regulating miR-3200 effectively blocked JNK and Wnt pathways likely via down-regulating AEG1. PEG10 knockdown played a carcinostatic role via up-regulating miR-3200 and further regulating AEG1 in gastric carcinoma cells, during which process, JNK pathway and Wnt pathway were blocked.

TGF-\u03b2 signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells

Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819.T cells compared with C28/I2 normal chondrocytes, while TGF-β1 treatment, mimicking higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting a negative association of PEG10 with malignant cartilage tumours. In chondrosarcoma cell lines, application of the TGF-β signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-β and BMP signalling, which are both SMAD pathways, whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-β signalling are mutually inhibitory in chondrosarcoma cells.

PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer

BackgroundOverexpression of paternally expressed gene-10 (PEG10) is known to promote the progression of several carcinomas, however, its role in pancreatic cancer (PC) is unknown. We investigated the expression and function of PEG10 in PC.MethodsPEG10 expression and correlation with PC progression was assessed in cancerous tissues and paired non-cancerous tissues. Further, the role of PEG10 in PC cell progression and the underlying mechanisms were studied by using small interfering RNA (Si-RNA).ResultsPEG10 expression was significantly higher in cancerous tissues and correlated with PC invasion of vessels and Ki-67 expression. Si-RNA mediated PEG10 knockdown resulted in inhibition of proliferation and G0/G1 cell cycle arrest, which was mediated by p21 and p27 upregulation. A decrease in PC cell invasion and migration, mediated by ERK/MMP7 pathway, was observed in PEG10 knockdown group. Further, findings of ChIP assay suggested that E2F-1 could directly enhance the expression of PEG10 through binding to PEG10 promoter.ConclusionsIn conclusion, PEG10 was identified as a prognostic biomarker for PC and E2F-1 induced PEG10 could promote PC cell proliferation, invasion, and metastasis.

MiR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC), a primary liver malignancy, is the most common cancer in males and fourth common cancer in females in Taiwan. HCC patients usually have a poor prognosis due to late diagnosis. It has been classified as a complex disease because of the heterogeneous phenotypic and genetic traits of the patients and a wide range of risk factors. Micro (mi)RNAs regulate oncogenes and tumor suppressor genes that are known to be dysregulated in HCC. Several studies have found an association between downregulation of miR-122, a liver-specific miRNA, and upregulation of paternally expressed gene 10 (PEG10) in HCC; however, the correlation between low miR-122 and high PEG10 levels still remains to be defined and require more investigations to evaluate their performance as an effective prognostic biomarker for HCC.MethodsAn in silico approach was used to isolate PEG10, a potential miR-122 target implicated in HCC development. miR-122S binding sites in the PEG10 promoter were evaluated with a reporter assay. The regulation of PEG10 by miR-122S overexpression was examined by quantitative RT-PCR, western blotting, and immunohistochemistry in miR-122 knockout mice and liver tissue from HCC patients. The relationship between PEG10 expression and clinicopathologic features of HCC patients was also evaluated.ResultsmiR-122 downregulated the expression of PEG10 protein through binding to 3′-untranslated region (UTR) of the PEG10 transcript. In miR-122 knockout mice and HCC patients, the deficiency of miR-122 was associated with HCC progression. The expression of PEG10 was increased in 57.3 % of HCC as compared to paired non-cancerous tissue samples. However, significant upregulation was detected in 56.5 % of patients and was correlated with Okuda stage (P = 0.05) and histological grade (P = 0.001).ConclusionsmiR-122 suppresses PEG10 expression via direct binding to the 3′-UTR of the PEG10 transcript. Therefore, while PEG10 could not be an ideal diagnostic biomarker for HCC but its upregulation in HCC tissue still has predictive value for HCC prognosis.

MP45-04 PATERNALLY EXPRESSED GENE-10 PROMOTES CELL GROWTH AND INVASION OF BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2016MP45-04 PATERNALLY EXPRESSED GENE-10 PROMOTES CELL GROWTH AND INVASION OF BLADDER CANCER Yoshihisa Kawai, Shusuke Akamatsu, Tetsutaro Hayashi, Eliana Beraldi, Fan Zhang, Roland Seiler, Jeffrey Leong, Htoo Oo, Igor Moskalev, Ladan Fazli, Hideyasu Matsuyama, Peter Black, Colin Collins, and Martin Gleave Yoshihisa KawaiYoshihisa Kawai More articles by this author , Shusuke AkamatsuShusuke Akamatsu More articles by this author , Tetsutaro HayashiTetsutaro Hayashi More articles by this author , Eliana BeraldiEliana Beraldi More articles by this author , Fan ZhangFan Zhang More articles by this author , Roland SeilerRoland Seiler More articles by this author , Jeffrey LeongJeffrey Leong More articles by this author , Htoo OoHtoo Oo More articles by this author , Igor MoskalevIgor Moskalev More articles by this author , Ladan FazliLadan Fazli More articles by this author , Hideyasu MatsuyamaHideyasu Matsuyama More articles by this author , Peter BlackPeter Black More articles by this author , Colin CollinsColin Collins More articles by this author , and Martin GleaveMartin Gleave More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.281AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have recently identified that paternally expressed gene-10 (PEG10) promotes cell cycle progression in the context of TP53 and RB1 loss in neuroendocrine prostate cancer. Based on the evidence that TP53 mutations and RB1 inactivation are more prevalent in muscle invasive bladder cancer (MIBC), it is possible that PEG10 may contribute to the progression and prognosis of MIBC. To test this hypothesis, we characterized PEG10 function in bladder cancer and evaluated if PEG10 can be a novel therapeutic target for these cancers. METHODS PEG10 gene expression of tumor samples was analyzed using the cancer genome atlas (TCGA) cohort. The PEG10 expression in several bladder cancer cell lines was assessed by Western blot analysis and quantitative reverse transcription-PCR (qRT-PCR). Silencing of PEG10 in vitro was achieved using siRNA. The in vivo effect of PEG10 antisense oligonucleotide (ASO) treatment was assessed in the T24 orthotopic bladder cancer model. RESULTS Higher mRNA level of PEG10 was significantly associated with poorer disease-free survival after cystectomy in 131 patients in the TCGA, Nature 2014 cohort. We examined PEG10 expression in a panel of 12 bladder cancer cell lines by Western blot. UM-UC14 showed the highest PEG10 expression, and T24 showed higher PEG10 expression than the other bladder cancer cell lines. Similar results were confirmed by qRT-PCR. PEG10 transient knockdown using two independent siRNAs resulted in significant growth suppression in UM-UC14 (RB1inactivatedTP53mut) and T24 (RB1wtTP53mut) cells. PEG10 knockdown induced higher expression of key cell cycle dependent kinase inhibitors p21 and p27 than observed in the control cells. Conversely, forced PEG10 RF1b/2 isoform over-expression induced cell growth in UC14 and T24 cells. Furthermore, UM-UC14 cell invasion was significantly decreased with PEG10 transient knockdown. Using BrdU incorporation assay after cell cycle synchronization by double-thymidine block, we found that PEG10 drove cell cycle progression from G0/G1. In the orthotopic bladder cancer model, systemic PEG10-ASO administration to athymic nude mice delayed tumor progression in T24 cells. CONCLUSIONS We have demonstrated that PEG10 promotes bladder cancer progression. Inhibition of PEG10 may be a novel treatment strategy for a subset of bladder cancer. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e608 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yoshihisa Kawai More articles by this author Shusuke Akamatsu More articles by this author Tetsutaro Hayashi More articles by this author Eliana Beraldi More articles by this author Fan Zhang More articles by this author Roland Seiler More articles by this author Jeffrey Leong More articles by this author Htoo Oo More articles by this author Igor Moskalev More articles by this author Ladan Fazli More articles by this author Hideyasu Matsuyama More articles by this author Peter Black More articles by this author Colin Collins More articles by this author Martin Gleave More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PEG10 plays a crucial role in human lung cancer proliferation, progression, prognosis and metastasis.

Paternally expressed gene 10 (PEG10) has been identified as a genetic imprinted gene, which is important for apoptosis resistance in cancer cells. Mounting evidence suggests that PEG10 is expressed in the majority of hepatocellular carcinoma (HCC) cells with growth-promoting activity. In the present study, we evaluated the correlation between PEG10 expression and the clinicopathological features of lung, breast and HCC tumors, and predicted the relationship between survival and expression levels of PEG10 in lung cancer patients. Furthermore, we chose non-small cell lung cancer cell line A549 as a model to analyze the function of PEG10 in proliferation and metastasis invitro. Our results revealed that expression of PEG10 was closely correlated with clinical TNM grade and patient prognosis in lung cancer. PEG10 enhanced cell proliferation and promoted tumor cell migration and invasion by upregulating the expression of β-catenin, MMP-2 and MMP-9, and decreased the expression of E-cadherin in the A549 cells. Our findings provide significant insight into the molecular mechanisms of lung cancer and offer novel ideas for designing new therapeutic targets for lung carcinoma.

Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia.

The aim of this study was to investigate the expression and significance of the imprinted gene PEG10 (paternally expressed gene 10) in preeclampsia placental tissue. Quantitative real-time reverse transcriptase polymerase chain reaction and immunohistochemistry to evaluate mRNA and protein expression and distribution of PEG10 in placental tissues obtained from 22 preeclampsia patients (8 patients with mild preeclampsia, 14 cases of severe preeclampsia). At the same time, 22 cases of normal pregnant women served as controls. PEG10 expression was determined in the placental tissue of the two different groups. In the normal pregnancy group, the average expression level of PEG10 was 0.5832 ± 0.045, while in the preeclampsia group, this level was 0.1943 ± 0.035. Statistical analysis showed that the two groups differed significantly (P < 0.05). The downregulated expression of the imprinted gene PEG10 may be an important reason for the occurrence of preeclampsia.

Molecular mechanism and function research of highly expressed PEG 10 gene in hepatocellular carcinoma

Objective: To study the molecular mechanism of dysregulation of PEG10 (paternally expressed gene 10), an imprinted gene in HCC (hepatocellular carcinoma), and to analyze its effect on the growth of hepatocellular carcinoma cells. Methods: The expression level of PEG10 mRNA was detected by semi-quantitative RT-PCR in 30 paired HCC/adjacent non-cancerous tissues and 15 types of liver cancer cell lines. Methylation status of CpG islands at the promoter of PEG10 gene in 17 paired HCC/adjacent non-cancerous tissue samples in which the expression of PEG10 gene in cancer tissues was significantly up-regulated as compared with non-cancerous tissues was detected using MSP (methylation specific PCR). The PEG10 shRNA (short hairpin RNA) was used to silence the expression of PEG10 gene in HCC QGY-7703 cells, and the colony-forming ability of QGY-7703 cells was detected by Western blotting and colony formation assay. Results: PEG10 mRNA expression level was significantly up-regulated in 67% (20/30) HCC tissues as compared with adjacent non-cancerous tissues. PEG10 was expressed in 15 types of HCC cell lines. The methylation status of PEG10 gene’s CpG2 island was significantly decreased in 29.4% (5/17) HCC tissue samples, and the overall decreased methylation status of PEG10 gene’s CpG2 island in HCC tissues was verified using bisulfite sequencing. Interestingly, silencing the expression of PEG10 in HCC QGY-7703 cells using shRNA targeting PEG10 gene markedly inhibited the colony-forming efficiency as compared with the HCC QGY-7703 cells transfected with negative control shRNA (P < 0.05). Conclusion: PEG10, an imprinted gene, is up-regulated in HCC, and may be closely related with the decreased methylation status of CpG2 island at the promoter of PEG10 gene. Silencing the expression of PEG10 can inhibit the growth of HCC cells, suggesting that PEG10 gene may play an important role in the hepatocarcinogenesis, and it may be used as a new marker or a potential therapeutic target for HCC. DOI:10.3781/j.issn.1000-7431.2013.01.005

PEG10 promotes the migration of human Burkitt’s lymphoma cells by up-regulating the expression of matrix metalloproteinase-2 and -9

Paternally expressed gene 10 (PEG10) is important for apoptosis resistance in cancer cells; however, the effect of PEG10 on tumor cell migration remains poorly understood. In this study, we investigated the effects of PEG10 on proliferation, apoptosis, adhesion and migration in the Burkitt's lymphoma cell line, Raji. Apoptosis was induced by 5-fluorouracil (5-FU) in pcDNA3.0/PEG10 transiently transfected HEK293T cells and PEG10-suppressed Raji cells. siRNAPEG10 was used to inhibit PEG10 expression. Fluorescence-activated cell sorting (FACS) were performed to analyze the effect of PEG10 on apoptosis. CCK-8 were performed to detect cell proliferation and adhesion. Matrigel invasion were performed using PEG10-suppressed Raji cells to investigate cell migration. The expression levels of matrix metalloproteinases -2and -9 (MMP-2 and MMP-9) were analyzed in PEG10-suppressed Raji cells using both real-time RT-PCR and Western blot analysis. HEK293T cells that overexpressed PEG10 exhibited greater viability 48 h following treatment with 5-FU, relative to control cells. Specific inhibition of PEG10 expression by siRNA resulted in inhibition of growth and apoptosis in Raji cells. Adherence and invasion capabilities were downregulated and expression levels of MMP-2 and MMP-9 were reduced in PEG10-suppressed Raji cells. Our findings demonstrated that PEG10 enhances the apoptotic resistance and viability of Raji cells. The migration and adherence invasion capacity of Raji cells could potentially be affected by regulation of the expression of MMP-2 and MMP-9. Our research provides a promising strategy for cancer immunotherapy of lymphoma.

Elevated expression of PEG10 in human placentas from preeclamptic pregnancies

The aim of this study was to determine qualitative and quantitative changes in paternally expressed gene 10 (PEG10) expression in preeclamptic placentas. Placental tissues were obtained immediately after delivery from women with normal pregnancies (n=20) and patients with preeclampsia (n=20). Quantitative real-time RT-PCR, Western blot analysis and immunohistochemistry were used to determine PEG10 gene expression and localization in placental tissues. Compared with the normal group, PEG10 was highly expressed at both mRNA and protein levels in preeclampsia (P<0.05). In immunohistochemical staining, PEG10 was present in the syncytiotrophoblast, cytotrophoblast, endothelial cell and stroma of all placentas. Notably, the intensity of PEG10 expression in the syncytiotrophoblast, cytotrophoblast and stem villi was much higher in preeclampsia than in normal. In conclusion, elevated expression of PEG10 is likely to be involved in the pathophysiology of preeclampsia. Further studies are needed to elucidate the precise role of PEG10 in preeclampsia.

Genetic imprinted gene PEG10 expression in deciduas of normal early pregnant women

Objective To investigate the role and significance of paternally expressed gene 10 (PEG10) in deciduas of normal pregnant women. Methods Sixty deciduas tissue from pregnant 6 to 11 weeks were divided into six groups and in each group ten samples were done every gestational week. The expression and distribution of PEG10 in deciduas were examined by RT-PCR, hybridization in situ, Western Blot and laser scanning confocal microscopy. Results The PEG10 mRNA and protein were expressed in deciduas tissue from pregnant 6 to 11 weeks. Among them, the expression of PEG10 showed a gradual increase as the pregnancy weeks increased. In RT-PCR, the PEG10 expression was lower at pregnant 6th week (0.6743±0.114), from pregnant 7 to 8 weeks, the expression was increased gradually (7th week 0.7349±0.0083) and reached the pinnacle at 8th week (0.7354±0.0074). And then the pinnacle began to descend (9th week 0.6340±0.0084, 10th week 0.5901±0.0089 and 11th week 0.5261±0.0112). There was a significant difference in the expression of PEG10 from pregnant 6 to 11 weeks except 7th week and 8th week. This expression characteristic was demonstrated by hybridization in situ. The similar conclusion was proved by Western Blot and laser scanning confocal microscopy. Conclusion Expression of PEG10 may play an important role in early pregnancy.

Genetic imprinted gene&lt;I&gt;PEG10&lt;/I&gt;expression in deciduas from inevitable abortion

The expression and distribution of the imprinted paternally expressed gene 10 (PEG10) in decidual tissues of 36 patients with inevitable abortion and 36 normal pregnant (NP) women were examined by RT-PCR, immunohistochemistry, in situ hybridization and Western blot. Decidual PEG10 mRNA expression was significantly lower in the patients than that in the NP group by RT-PCR (P<0.05). The characteristic PEG10 expression was confirmed by in situ hybridization. As shown by Western blot and immunohistochemistry, PEG10 protein expression was consistent with the mRNA expression pattern. The results showed that maintaining sufficient levels of PEG10 may be important during early pregnancy. Lower levels of PEG10 might be one of reasons that underlie inevitable abortion.