An Eye into the Aorta: The Role of Extracellular Matrix Regulatory Genes ZNF469 and PRDM5, from Their Previous Association with Brittle Cornea Syndrome to Their Novel Association with Aortic and Arterial Aneurysmal Diseases.

The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes' development of aneurysmal and dissection diseases.

Circ_PRDM5/miR-25-3p/ANKRD46 axis is associated with cell malignant behaviors in subjects with breast cancer evaluated by ultrasound.

Circular RNAs (circRNAs) are key RNA molecules in cancer biology. CircRNA PR/SET domain 5 (circ_PRDM5, hsa_circ_0005654) was downregulated in breast cancer (BC) tissues. This study is designed to investigate the functional mechanism of circ_PRDM5 in BC. Ultrasound examinations were performed to evaluate BC patients and normal individuals. Circ_PRDM5, miR-25-3p, and Ankyrin repeat domain 46 (ANKRD46) level detection was carried out by reverse transcription-quantitative polymerase chain reaction. 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used for cell viability examination. Cell proliferation was evaluated by ethynyl-2'-deoxyuridine assay and colony formation assay. The protein levels were examined using western blot. Cell migration and invasion abilities were assessed via transwell assay. Target interaction was analyzed via dual-luciferase reporter assay. The role of circ_PRDM5 in vivo was explored via xenograft tumor assay. Circ_PRDM5 expression was downregulated in BC tissues and cells. Overexpression of circ_PRDM5 suppressed proliferation and motility but enhanced apoptosis of BC cells. Circ_PRDM5 served as a sponge of miR-25-3p. Circ_PRDM5 impeded BC cell malignant development via sponging miR-25-3p. Circ_PRDM5 induced ANKRD46 upregulation by targeting miR-25-3p. Inhibition of miR-25-3p retarded BC progression by increasing the ANKRD46 level. Circ_PRDM5 repressed BC tumorigenesis in vivo through mediating the miR-25-3p/ANKRD46 axis. This study evidenced that circ_PRDM5 inhibited cell progression and tumor growth in BC via interacting with mir-25-3p/ANKRD46 network.

Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: The role of the PRDM5 in esophageal squamous cell carcinoma (ESCC) has not been revealed. This study investigated the relationship between PRDM5 expression and survival outcome in esophageal squamous cell carcinoma and explored the mechanism in tumor development. METHODS: In present study, expression of PRDM5 mRNA in esophageal squamous cell carcinoma patients was conducted using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The expression of PRDM5 was assessed by immunohistochemical staining. Kaplan-Meier curve and Cox regression analysis was performed to analyze the survival outcome and independent predictive factors. qRT-PCR and Methylation-specific PCR were performed to identify the mRNA level of PRDM5 and Methylation rate. Cibersort algorithm to analyze the relationship between PRDM5 expression and immune cell invasion. Western-blot was performed to confirm the expression of esophageal tumor tissues and adjacent tissues. RESULTS: The TCGA database and GEO database show that PRDM5 mRNA level in esophageal squamous cell carcinoma adjacent tissues was higher than that of cancer tissues, and ESCC patients with high expression of PRDM5 mRNA had better overall survival. Tissue microarray showed that the protein level of PRDM5 in the adjacent tissues of patients with ESCC was higher than that in cancer tissues, and the expression level of PRDM5 was significantly correlated with the grade of clinicopathological characteristics (P < 0.001). Patients with high expression of PRDM5 displayed a better OS and DFS. Cox regression analysis showed that PRDM5 was an independent risk factor and prognostic factor for ESCC patients (HR: 2.626, 95%CI: 1.824-3.781; P < 0.001). The protein level of PRDM5 matched with the transcriptional level, whereas the DNA methylation affected the transcriptional level. Cibersort showed that T cells CD4 memory resting, mast cells resting, eosinophils, M2 macrophages and mast cells activated were significantly positively correlated with PRDM5 expression (P < 0.05), while regulatory T cells, monocytes and dendritic cells negatively correlated with PRDM5 expression (P < 0.05). CONCLUSION: PRDM5 can be used as a biomarker to predict the survival of ESCC patients. Furthermore, PRDM5 expression in ESCC cells may affect WNT/ß-catenin signaling pathways, thus further affect the ESCC cell proliferation, migration, and invasion capacity.

More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome.

Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder characterized by corneal thinning and fragility, leading to corneal rupture, the main hallmark of this disorder. Non-ocular symptoms include not only hearing loss but also signs of connective tissue fragility, placing it in the Ehlers-Danlos syndrome (EDS) spectrum. It is caused by biallelic pathogenic variants in ZNF469 or PRDM5, which presumably encode transcription factors for extracellular matrix components. We report the clinical and molecular features of nine novel BCS families, four of which harbor variants in ZNF469 and five in PRDM5. We also performed a genotype- and phenotype-oriented literature overview of all (n = 85) reported patients with ZNF469 (n = 53) and PRDM5 (n = 32) variants. Musculoskeletal findings may be the main reason for referral and often raise suspicion of another heritable connective tissue disorder, such as kyphoscoliotic EDS, osteogenesis imperfecta, or Marfan syndrome, especially when a corneal rupture has not yet occurred. Our findings highlight the multisystemic nature of BCS and validate its inclusion in the EDS classification. Importantly, gene panels for heritable connective tissue disorders should include ZNF469 and PRDM5 to allow for timely diagnosis and appropriate preventive measures for this rare condition.

Silencing of PRDM5 increases cell proliferation and inhibits cell apoptosis in glioma.

AIM: PR-domain-containing 5 (PRDM5), a family member of PR-domain-containing zinc finger genes, has been reported to participate in modulate cellular processes, including cell growth, differentiation and apoptosis. It has also been found to function as a putative tumor suppressor in different types of cancer. The present study is the first, to the best of our knowledge, to report on the clinical significance of the expression of PRDM5 in glioma cell line. MATERIALS AND METHODS: Western blot analyse the expression of PRDM5 in glioma tissues and cells. 80 tissues microarray samples from patients with glioma were examined using immunohistochemical analysis. Glioblastoma U251 cells were transfected with PRDM5-siRNA and control-siRNA. U251cell proliferation was measured by flow cytometric analysis and plate colony formation assay. Cell apoptosis were detected using flow cytometric analysis. RESULTS: The results of western blot analysis and immunohistochemistry showed that the expression of PRDM5 was decreased in fresh glioma tissues, compared with that in normal brain tissues. Kaplan-Meier postoperative survival curves demonstrated that the low expression of PRDM5 was associated with poor prognosis in patients with glioma. In addition, suppression of PRDM5 promoted cell proliferation via regulating cell cycle progression. Finally, knocking down PRDM5 using small interfering RNA decreased the apoptosis of glioma cells. CONCLUSION: Taken together, these findings suggested that PRDM5 may be a novel therapeutic target of glioma.

Knockdown of lncRNA BDNF-AS suppresses neuronal cell apoptosis via downregulating miR-130b-5p target gene PRDM5 in acute spinal cord injury.

OBJECTIVE: The present study was designed to investigate the molecular mechanism and biological roles of lncRNA brain-derived neurotrophic factor antisense (lncRNA BDNF-AS) in acute spinal cord injury (ASCI). METHODS: The rat model of ASCI and hypoxic cellular model were established to detect the expression of BDNF-AS, miR-130b-5p, PR (PRDI-BF1 and RIZ) domain protein 5 (PRDM5) and cleaved caspase 3 (c-caspase 3) using qRT-PCR and western blot. Basso, Beattie and Bresnahan (BBB) score was carried out to assess neurological function. Flow cytometry was used to determine the apoptosis of neuronal cells. The association among BDNF-AS, miR-130b-5p and PRDM5 were disclosed by RNA immunoprecipitation (RIP) assay, RNA pull-down assay and dual-luciferase reporter assay. RESULTS: BDNF-AS, PRDM5 and c-caspase 3 expression were significantly upregulated, while miR-130b-5p was suppressed in the ASCI group and neuronal cells following hypoxia treatment. BDNF-AS knockdown inhibited neuronal cell apoptosis. Further studies indicated that BDNF-AS functioned as a competing endogenous RNA (ceRNA) by sponging miR-130b-5p in neuronal cells. Further investigations demonstrated that PRDM5 was a target of miR-130b-5p and BDNF-AS knockdown exerted anti-apoptotic effects via miR-130b-5p/PRDM5 axis. CONCLUSION: The lncRNA BDNF-AS/miR-130b-5p/PRDM5 axis might be a promising therapeutic target for ASCI.

A causal relationship between the neurotherapeutic effects of miR182/7a and decreased expression of PRDM5.

BACKGROUND: Spinal cord injury (SCI) is terrible damage resulting in the deficiencies and necrosis of neurology and causes infinite inconvenience to sufferers. The therapy of SCI still meets a larger number of problems. Therefore, the underlying mechanism and novel therapy of acute SCI (ASCI) are urgent to explore. MATERIALS AND METHODS: The SCI model was established in rats. The expression of miR-182/miR-7a and PRDM5 at mRNA level was detected by quantitative real-time PCR and the protein expression of PRDM5 and c-caspase 3 was assessed by western blotting assays. The apoptosis of spinal cord neurons (SCN) was assessed on flow cytometry. The transfection of cells was performed by Lipofectamine 2000 kit. The relationship between PRDM5 and miR-182/miR-7a was examined by Luciferase assay. RESULTS: The expression of PRDM5 was up-regulated at either mRNA (2.212 folds) or protein level after SCI in rats, and knockdown of PRDM5 in SCN declined the c-caspase3 expression. In addition, the expression of miR-182 and miR-7a was decreased by 44.6% and 39.3% after SCI in rats. Moreover, the expression of miR-182 and miR-7a were negatively correlated with the level of PRDM5 expression, and the expression of PRDM5 was inhibited due to the increase of miR-182 and/or miR-7a expression. Moreover, both miR-182 and miR-7a could regulate PRDM5 to control SCN apoptosis. According to the BBB score increased 2 folds, the intrathecal injection of miR-182 and miR-7a improved the neurological function of rats. CONCLUSION: Inhibition of PRDM5 which was apparently negative correlation with miR-182 and miR-7a could suppress the neurons apoptosis to attenuate acute spinal cord injury in rats.

Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye, often leading to secondary glaucoma and several systemic malformations. It is inherited in an autosomal dominant fashion that has been associated with genetic defects in PITX2 and FOXC1. Known genes CYP1b1, PITX2, and FOXC1 were excluded by Sanger sequencing. The purpose of current study is to identify the underlying genetic causes in ARS family by whole exome sequencing (WES). WES was performed for affected proband of family, and variants were prioritized based on in silico analyses. Segregation analysis of candidate variants was performed in family members. A novel heterozygous PRDM5 missense variant (c.877A>G; p.Lys293Glu) was found to segregate with the disease in an autosomal dominant fashion. The novel missense variant was absent from population-matched controls, the Exome Variant Server, and an in-house exome variant database. The Lys293Glu variant is predicted to be pathogenic and affects a lysine residue that is conserved in different species. Variants in the PRDM5 gene were previously identified in anterior segment defects, i.e., autosomal recessive brittle cornea syndrome and keratoconus. The results of this study suggest that genetic variants in PRDM5 can lead to various syndromic and nonsyndromic disorders affecting the anterior segment of the eye.

Deregulation of PRDM5 promotes cell proliferation by regulating JAK/STAT signaling pathway through SOCS1 in human lung adenocarcinoma.

BACKGROUND: PRDM5 is considered a tumor suppressor in several types of solid tumors and is involved in multiple cellular processes. However, target genes regulated by PRDM5 in lung cancer and its potential mechanism are poorly defined. METHODS: Survival analysis was conducted using Kaplan-Meier estimates based on the online databases. RNA-sequencing and bioinformatics analysis were performed to identify the differentially expressed genes in PRDM5-overexpressed A549 cells. RESULTS: We observed deregulated PRDM5 in several lung adenocarcinoma cell lines and its association with a poor prognosis. PRDM5 overexpression inhibited the proliferation of lung adenocarcinoma cells in vitro and suppressed tumor growth in a xenograft model. PRDM5 upregulated the promoter activity of SOCS1, which then inhibited the phosphorylation of JAK2 and STAT3. CONCLUSIONS: Our study suggests that the low expression of PRDM5 promotes the proliferation of lung adenocarcinoma cells by downregulating SOCS1 and then upregulating the JAK2/STAT3 signaling pathway.

Homozygous Val6Gly Variation in PRDM5 Gene Causing Brittle Cornea Syndrome: A New Turkish Case.

Introduction: Brittle cornea syndrome (BCS) is a rare connective tissue disorder with ocular and systemic features. Extreme corneal thinning and fragility are the main hallmarks of BCS. Case Report: A 4-year-old boy presented with recurrent spontaneous corneal perforation. He had blue sclera, corneal leucoma, irregular iris, shallow anterior chamber, corneal astigmatism, and bilateral corneal thinning. He also had several systemic features including hearing loss, skin hyperelasticity, joint hypermobility, scoliosis, and umbilical hernia. A diagnosis of BCS was confirmed with molecular analysis. A homozygous c.17T>G, p.(Val6Gly) variation was identified in the PRDM5 gene. Discussion: p.(Val6Gly) variation in PRDM5 was previously reported in 2 patients with BCS. We also considered PRDM5 c.17T>G, p.(Val6Gly) variation as pathogenic based on the following features: the absence of the variation in population databases, in silico predictions, segregation analysis, and clinical signs of our patient. Extremely thin and brittle corneas lead to corneal perforation spontaneously or after minor trauma. Nearly all patients have lost their vision because of corneal rupture and scars. The key challenge in the management of BCS is the prevention of ocular rupture which relies on early diagnosis. Early diagnosis allows for taking prompt measures to prevent ocular rupture.

The Association of Novel Single-Nucleotide Variants in the Collagen Matrix-Encoding Gene PRDM5 with Aortic Aneurysmal Disease.

Thoracic aortic aneurysms are clinical conditions that are associated with severe clinical endpoints including dissection and rupture, potentially leading to sudden death. Contrary to their abdominal counterparts, thoracic aortic aneurysms are well-recognized to have a genetic basis underlying their development. Among all patients with aneurysmal disease who underwent clinical genetic screening in our program (N = 145), two patients were found to have variants of uncertain significance (VUS) in the PRDM5 gene. This gene is responsible for multiple regulatory functions in extracellular matrix development, and this is the first report, to our knowledge, to associate this gene with aortopathy.

TGF-ß2-induced circ-PRDM5 regulates migration, invasion, and EMT through the miR-92b-3p/COL1A2 pathway in human lens epithelial cells.

CircRNA circ-PRDM5 (PR/SET domain 5) (circ-PRDM5) is overexpressed in age-related cataracts. Nevertheless, the biological role of circ-PRDM5 in posterior capsule opacities (PCO) (a common complication after cataract surgery) is unclear. Human lens epithelial cells SRA01/04 (LECs) were stimulated with TGF-ß2 (transforming growth factor beta-2) to mimic the PCO model in vitro. Cell viability, migration, and invasion were determined by MTT, transwell, or wound-healing assays. Protein levels of EMT (epithelial-to-mesenchymal transition) markers and COL1A2 (collagen type I alpha 2 chain) were analyzed by western blotting (WB). Relative expression of circ-PRDM5, miR-92b-3p, and COL1A2 mRNA was analyzed by qRT-PCR. The targeting relationship was confirmed by dual-luciferase reporter and RIP assays. We observed that circ-PRDM5 and COL1A2 were upregulated in PCO tissues and TGF-ß2-treated LECs, while miR-92b-3p was downregulated. Both circ-PRDM5 and COL1A2 knockdown impaired TGF-ß2-induced LEC migration, invasion, and EMT. Also, circ-PRDM5 could adsorb miR-92b-3p to regulate COL1A2 expression. Furthermore, miR-92b-3p inhibitor offset circ-PRDM5 knockdown-mediated influence on migration, invasion, and EMT of LECs under TGF-ß2 stimulation. Also, COL1A2 overexpression overturned the repressive influence of miR-92b-3p mimic on TGF-ß2-induced LEC migration, invasion, and EMT. In summary, TGF-ß2-induced circ-PRDM5 facilitated LEC migration, invasion, and EMT by adsorbing miR-92b-3p and increasing COL1A2 expression, offering new insights into the development of PCO.

Downregulation of promoter methylation gene PRDM5 contributes to the development of tumor proliferation and predicts poor prognosis in gastric cancer.

Background: Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Previous studies have shown that PRDM5 is methylated and silenced in GC. However, the role of PRDM5 in GC progression has not been explored. Methods: The expression and epigenetic alterations of PRDM5 in GC were analyzed in public datasets. The mRNA and protein expression of PRDM5 in fresh tissues were detected by semi-quantitative PCR and Western blot. And expression of PRDM5 in gastric paracarcinoma and carcinoma tissues from 162 patients was detected by immunohistochemistry (IHC) and assessed the association with different clinicopathological features. The prognostic value of PRDM5 in GC patients was evaluated using Kaplan-Meier plotter. We also studied promoter region methylation of PRDM5 in GC by methylation-specific PCR (MSP). The effects of PRDM5 on cell proliferation and migration were conducted by functional experiments in vitro. Results: The expression of PRDM5 was downregulated in GC, and that was associated with poor survival and tumor progression. And PRDM5 expression was found to be an independent prognostic factor for GC. We also found that the methylation of PRDM5 promoter was closely related to the histopathological types and the progression of tumors through the public relations database. In vitro, ectopical expression of PRDM5 inhibited the growth of tumor cells, while knockdown of PRDM5 increased the proliferation and migration of tumor cells. Conclusion: These results suggest that PRDM5 may be a novel TSG methylated in GC that plays important roles in GC development. And we found PRDM5 as a potential survival biomarker for GC, especially in well differentiated GC. PRDM5 expression was significantly correlated with tumor stage and histological type.

miR-495 reduces neuronal cell apoptosis and relieves acute spinal cord injury through inhibiting PRDM5.

This study aims to investigate the role of miR-495 in neuronal cell apoptosis after acute spinal cord injury (ASCI). The ASCI rat model was established and the Basso, Beattie, and Bresnahan (BBB) score was assessed. miR-495, PR domain containing 5 (PRDM5), and Bcl-2 expressions were measured by qRT-PCR or western blotting. Neuronal cell line PC-12 was subjected to hypoxia condition to simulate the in vitro ASCI model. PC-12 cell apoptosis was measured by flow cytometry, and the interaction between miR-495 and PRDM5 was confirmed by dual luciferase reporter assay. Results showed that BBB score was significantly decreased in ASCI rats compared with sham rats. miR-495 expression was down-regulated in spinal cord tissue of ASCI rats and hypoxia-induced PC-12 cells, and PRDM5 protein level was up-regulated in spinal cord tissue of ASCI rats and hypoxia-induced PC-12 cells. miR-495 overexpression could reduce apoptosis of PC-12 cells, and up-regulated anti-apoptosis protein Bcl-2 protein level. Moreover, PRDM5 was a target of miR-495, and mRNA and protein levels of PRDM5 were negatively regulated by miR-495. miR-495 overexpression could reduce the hypoxia-induced PC-12 cell apoptosis, while PRDM5 overexpression abolished this inhibiting effect. The agomir-495 was injected into ASCI rats, and Bcl-2 protein level and BBB score were increased, but the PRDM5 overexpression reversed these results. Overall, we concluded that miR-495 could inhibit neuronal cell apoptosis and relieve acute spinal cord injury through inhibiting PRDM5.

Overexpression of PRDM5 promotes acute myeloid leukemia cell proliferation and migration by activating the JNK pathway.

PRDM family proteins are dysregulated in many human diseases, especially hematological malignancies and solid cancers, and share a unique N-terminal PR domain followed by zinc fingers toward the C terminus. With a high frequency of DNA promoter hypermethylation, PRDM5 is primarily considered as a tumor suppressor in solid tumors. However, little is known about the function of PRDM5 in blood malignancies, especially acute myeloid leukemia (AML). In this study, we showed that high PRDM5 expression levels were independently correlated with poor overall survival in AML patients. PRDM5 overexpression promoted cell proliferation, colony formation, and migration in vitro and enhanced tumorigenesis in an in vivo xenograft model. Furthermore, we found that PRDM5 overexpression promoted cell cycle progression with the decreased level of cell cycle inhibitors such as p16 and p21, and regulated the expression of epithelial-mesenchymal transition markers ZO-1 and Vimentin to promote migration. Moreover, we observed that PRDM5 upregulated the Jun N-terminal kinase (JNK) signaling pathway and downregulated c-Myc expression. Pharmacological inhibition of JNK by SP600125 partially abrogated PRDM5-induced cell proliferation and migration. Taken together, our findings demonstrate that PRDM5 functions as an oncogenic driver in AML via JNK pathway, suggesting that PRDM5 is a potential therapeutic target for AML.

PRDM5 promotes the apoptosis of epithelial cells induced by IFN-γ during Crohn's disease.

Elevated apoptosis of intestinal epithelial cells (IECs) greatly impairs the epithelial barrier integrity and contributes to the pathogenesis of Crohn's Disease (CD). Overproduction of pro-inflammatory cytokine Interferon-γ (IFN-γ) induces the excessive apoptosis of IECs and is involved in CD development. PRDM5 (PR domain containing 5 PFM2) a member of PRDM family, reportedly acts as a transcriptional regulator involved in tissue specific differentiation and tumor development. In this study, we investigated PRDM5 expression and its potential functions in both human CD (Crohn's disease) and TNBS (2,4,6-trinitrobenzenesulfonic acid sol)-induced mice experimental colitis. As shown by western blot and immunohistochemistry, significant up-regulation of PRDM5 was found in the inflamed intestinal tissues of CD patients and TNBS-treated mice, and the molecule was mainly located in IECs. To explore the biological functions of PRDM5 in IEC apoptosis, we established the interferon-γ (IFN-γ) induced cellular apoptosis model on human IEC line HT29 in vitro. IFN-γ significantly increased the expression of PRDM5 in a both time-dependent and concentration-dependent manner in HT29 cells, which was accompanied with an up-regulated expression of apoptotic markers (active caspase-3 and cleaved PARP(poly (ADP-ribpse) polymerase)). Inhibiting PRDM5 expression by siRNA attenuated the IFN-γ-triggered accumulation of active caspase-3 and cleaved PARP in IECs. Moreover, flow cytometry assay and CCK-8 analysis revealed that PRDM5 knockdown significantly alleviated the IFN-γ-induced cellular apoptosis in HT29 cells. Taken together, these data suggest that highly expressed PRDM5 may promote the IFN-γ-induced IEC apoptosis in the progression of CD.

PRDM5 promotes the proliferation and invasion of murine melanoma cells through up-regulating JNK expression.

PRDM (PRDI-BF1 and RIZ domain-containing) proteins constitute a family of zinc finger proteins and play important roles in multiple cellular processes by acting as epigenetic modifiers. PRDM5 is a recently identified member of the PRDM family and may function as a tumor suppressor in several types of cancer. However, the role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of PRDM5 on murine melanoma cells was determined and results showed that PRDM5 overexpression significantly promoted proliferation, migration, and invasion of murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression significantly inhibited proliferation, invasion, and migration of B16F10 cells. In vivo study also showed that PRDM5 silencing significantly inhibited the growth and metastasis of melanoma in mice. PRDM5 was then found to increase the expression and activation of JNK in B16F10 cells. JNK silencing significantly reduced PRDM5-mediated up-regulation of JNK expression and blocked the PRDM5-induced proliferation and invasion of B16F10 cells. To further verify the involvement of JNK signaling in PRDM5-induced progression of B16F10 cells, a specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and results showed that PRDM5-induced proliferation and invasion of B16F10 cells were abolished. We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up-regulating JNK expression and strategies targeting PRDM5 may be promising for the therapy of melanoma.

Upregulation of PRDM5 Is Associated with Astrocyte Proliferation and Neuronal Apoptosis Caused by Lipopolysaccharide.

PRDM5 (PR domain containing 5) belongs to PRDM family which consists of transcriptional regulators that modulate cellular processes such as cell growth, differentiation and apoptosis. However, the function of PRDM5 in central nervous system (CNS) inflammatory response is unknown. In recent study, an adult rat neuroinflammation model via lipopolysaccharide (LPS) lateral ventricle injection was constructed. PRDM5 expression was increased in activated astrocytes and apoptotic neurons of the adult rat cerebral cortex after LPS injection. In vitro studies showed that the remarkable upregulation of PRDM5 might be involved in rat primary astrocyte proliferation and rat primary neuronal apoptosis in the cerebral cortex following LPS administration. In addition, using PRDM5 RNA interference both in rat primary asrtocytes and neurons, further indicated that PRDM5 was required for astrocyte proliferation and neuronal apoptosis induced by LPS. Our findings on the cellular signaling pathway may provide a new therapeutic strategy against neuroinflammation in the CNS.

Gene methylation in gastric cancer.

Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field.