Epigenetic Regulation of Ameloblast Differentiation by HMGN Proteins.

Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.

HMGN5 Escorts Oncogenic STAT3 Signaling by Regulating the Chromatin Landscape in Breast Cancer Tumorigenesis.

Cancer progression is highly dependent on the ability of cancer cell tumor formation, in which epigenetic modulation plays an essential role. However, the epigenetic factors promoting breast tumor formation are less known. Screened from three-dimensional (3D)-sphere tumor formation model, HMGN5 that regulates chromatin structures became the candidate therapeutic target in breast cancer, though its role is obscure. HMGN5 is highly expressed in 3D-spheres of breast cancer cells and clinical tumors, also an unfavorable prognostic marker in patients. Furthermore, HMGN5 controls tumor formation and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape the oncogenic chromatin landscape and transcriptional program. More importantly, interference of HMGN5 by nanovehicle-packaged siRNA effectively inhibits tumor growth in breast cancer cell-derived xenograft mice model. IMPLICATIONS: Our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic target in STAT3-hyperactive breast cancer.

HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer.

High-mobility group nucleosome-binding domain 4 (HMGN4) exerts biological functions by regulating gene transcription through binding with nucleosome. As a new epigenetic regulator discovered in 2001, its biological functions have not been clarified. HMGN4 belongs to HMGNs family, in which HMGN1, 2 and 5 have been reported to play roles in oncogenesis of various cancers. However, it is reported that HMGN4 was associated with thyroid and liver cancer. In this study, we discovered for the first time that HMGN4 was highly expressed in human triple-negative breast cancer (TNBC), based on the analysis of the TCGA database. Moreover, we found that HMGN4 controlled the proliferation of human TNBC cells both in vitro and in vivo. Mechanistically, the positive correlation occurred between HMGN4 and STAT3 downstream genes while HMGN4 played an indispensable role in constitutively active STAT3 (STAT3C) induced colony formation. Interestingly, we reported that STAT3 regulated HMGN4 transcription as its transcriptional factor by chromatin immunoprecipitation and HMGN4 promoter-luc assays. That is to say, there is a feed-forward signaling circuit between HMGN4 and STAT3, which might control TNBC cell growth. Finally, we proved that the interference of HMGN4 by nanovehicle-packaged siRNA may be a potentially effective approach in TNBC treatment. In summary, our findings not only identified a novel regulator in TNBC cell proliferation but also revealed the mechanism by which HMGN4 acted as a downstream gene of STAT3 to participate in the STAT3 pathway, which indicated that HMGN4 was likely to be a potential novel target for anti-TNBC therapy.

Multiple epigenetic factors co-localize with HMGN proteins in A-compartment chromatin.

BACKGROUND: Nucleosomal binding proteins, HMGN, is a family of chromatin architectural proteins that are expressed in all vertebrate nuclei. Although previous studies have discovered that HMGN proteins have important roles in gene regulation and chromatin accessibility, whether and how HMGN proteins affect higher order chromatin status remains unknown. RESULTS: We examined the roles that HMGN1 and HMGN2 proteins play in higher order chromatin structures in three different cell types. We interrogated data generated in situ, using several techniques, including Hi-C, Promoter Capture Hi-C, ChIP-seq, and ChIP-MS. Our results show that HMGN proteins occupy the A compartment in the 3D nucleus space. In particular, HMGN proteins occupy genomic regions involved in cell-type-specific long-range promoter-enhancer interactions. Interestingly, depletion of HMGN proteins in the three different cell types does not cause structural changes in higher order chromatin, i.e., in topologically associated domains (TADs) and in A/B compartment scores. Using ChIP-seq combined with mass spectrometry, we discovered protein partners that are directly associated with or neighbors of HMGNs on nucleosomes. CONCLUSIONS: We determined how HMGN chromatin architectural proteins are positioned within a 3D nucleus space, including the identification of their binding partners in mononucleosomes. Our research indicates that HMGN proteins localize to active chromatin compartments but do not have major effects on 3D higher order chromatin structure and that their binding to chromatin is not dependent on specific protein partners.

HMGN3 represses transcription of epithelial regulators to promote migration of cholangiocarcinoma in a SNAI2-dependent manner.

High mobility group nucleosome-binding protein 3 (HMGN3), a member of the HMGN family, modulates the structure of chromatin and regulates transcription through transcription factors. HMGN3 has been implicated in the development of various cancers; however, the underlying mechanisms remain unclear. We herein demonstrated that the high expression of HMGN3 correlated with the metastasis of liver fluke infection-induced cholangiocarcinoma (CCA) in patients in northeastern Thailand. The knockdown of HMGN3 in CCA cells significantly impaired the oncogenic properties of colony formation, migration, and invasion. HMGN3 inhibited the expression of and blocked the intracellular polarities of epithelial regulator genes, such as the CDH1/E-cadherin and TJAP1 genes in CCA cells. A chromatin immunoprecipitation sequencing analysis revealed that HMGN3 required the transcription factor SNAI2 to bind to and repress the expression of epithelial regulator genes, at least in part, due to histone deacetylases (HDACs), the pharmacological inhibition of which reactivated these epithelial regulators in CCA, leading to impairing the cell migration capacity. Therefore, the overexpression of HMGN3 represses the transcription of and blocks the polarities of epithelial regulators in CCA cells in a manner that is dependent on the SNAI2 gene and HDACs.

H3K27ac nucleosomes facilitate HMGN localization at regulatory sites to modulate chromatin binding of transcription factors.

Nucleosomes containing acetylated H3K27 are a major epigenetic mark of active chromatin and identify cell-type specific chromatin regulatory regions which serve as binding sites for transcription factors. Here we show that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 bind preferentially to H3K27ac nucleosomes at cell-type specific chromatin regulatory regions. HMGNs bind directly to the acetylated nucleosome; the H3K27ac residue and linker DNA facilitate the preferential binding of HMGNs to the modified nucleosomes. Loss of HMGNs increases the levels of H3K27me3 and the histone H1 occupancy at enhancers and promoters and alters the interaction of transcription factors with chromatin. These experiments indicate that the H3K27ac epigenetic mark enhances the interaction of architectural protein with chromatin regulatory sites and identify determinants that facilitate the localization of HMGN proteins at regulatory sites to modulate cell-type specific gene expression.

Spatial and Temporal Expression of High-Mobility-Group Nucleosome-Binding (HMGN) Genes in Brain Areas Associated with Cognition in Individuals with Down Syndrome.

DNA methylation and histone posttranslational modifications are epigenetics processes that contribute to neurophenotype of Down Syndrome (DS). Previous reports present strong evidence that nonhistone high-mobility-group N proteins (HMGN) are epigenetic regulators. They play important functions in various process to maintain homeostasis in the brain. We aimed to analyze the differential expression of five human HMGN genes in some brain structures and age ranks from DS postmortem brain samples. Methodology: We performed a computational analysis of the expression of human HMGN from the data of a DNA microarray experiment (GEO database ID GSE59630). Using the transformed log2 data, we analyzed the differential expression of five HMGN genes in several brain areas associated with cognition in patients with DS. Moreover, using information from different genome databases, we explored the co-expression and protein interactions of HMNGs with the histones of nucleosome core particle and linker H1 histone. Results: We registered that HMGN1 and HMGN5 were significantly overexpressed in the hippocampus and areas of prefrontal cortex including DFC, OFC, and VFC of DS patients. Age-rank comparisons between euploid control and DS individuals showed that HMGN2 and HMGN4 were overexpressed in the DS brain at 16 to 22 gestation weeks. From the BioGRID database, we registered high interaction scores of HMGN2 and HMGN4 with Hist1H1A and Hist1H3A. Conclusions: Overall, our results give strong evidence to propose that DS would be an epigenetics-based aneuploidy. Remodeling brain chromatin by HMGN1 and HMGN5 would be an essential pathway in the modification of brain homeostasis in DS.

Testing mechanisms of DNA sliding by architectural DNA-binding proteins: dynamics of single wild-type and mutant protein molecules in vitro and in vivo.

Architectural DNA-binding proteins (ADBPs) are abundant constituents of eukaryotic or bacterial chromosomes that bind DNA promiscuously and function in diverse DNA reactions. They generate large conformational changes in DNA upon binding yet can slide along DNA when searching for functional binding sites. Here we investigate the mechanism by which ADBPs diffuse on DNA by single-molecule analyses of mutant proteins rationally chosen to distinguish between rotation-coupled diffusion and DNA surface sliding after transient unbinding from the groove(s). The properties of yeast Nhp6A mutant proteins, combined with molecular dynamics simulations, suggest Nhp6A switches between two binding modes: a static state, in which the HMGB domain is bound within the minor groove with the DNA highly bent, and a mobile state, where the protein is traveling along the DNA surface by means of its flexible N-terminal basic arm. The behaviors of Fis mutants, a bacterial nucleoid-associated helix-turn-helix dimer, are best explained by mobile proteins unbinding from the major groove and diffusing along the DNA surface. Nhp6A, Fis, and bacterial HU are all near exclusively associated with the chromosome, as packaged within the bacterial nucleoid, and can be modeled by three diffusion modes where HU exhibits the fastest and Fis the slowest diffusion.

Telomere-to-telomere assembly of a fish Y chromosome reveals the origin of a young sex chromosome pair.

BACKGROUND: The origin of sex chromosomes requires the establishment of recombination suppression between the proto-sex chromosomes. In many fish species, the sex chromosome pair is homomorphic with a recent origin, providing species for studying how and why recombination suppression evolved in the initial stages of sex chromosome differentiation, but this requires accurate sequence assembly of the X and Y (or Z and W) chromosomes, which may be difficult if they are recently diverged. RESULTS: Here we produce a haplotype-resolved genome assembly of zig-zag eel (Mastacembelus armatus), an aquaculture fish, at the chromosomal scale. The diploid assembly is nearly gap-free, and in most chromosomes, we resolve the centromeric and subtelomeric heterochromatic sequences. In particular, the Y chromosome, including its highly repetitive short arm, has zero gaps. Using resequencing data, we identify a ~7 Mb fully sex-linked region (SLR), spanning the sex chromosome centromere and almost entirely embedded in the pericentromeric heterochromatin. The SLRs on the X and Y chromosomes are almost identical in sequence and gene content, but both are repetitive and heterochromatic, consistent with zero or low recombination. We further identify an HMG-domain containing gene HMGN6 in the SLR as a candidate sex-determining gene that is expressed at the onset of testis development. CONCLUSIONS: Our study supports the idea that preexisting regions of low recombination, such as pericentromeric regions, can give rise to SLR in the absence of structural variations between the proto-sex chromosomes.

HMGN5 promotes invasion and migration of colorectal cancer through activating FGF/FGFR pathway.

OBJECTIVE: To detect the expression of high-mobility group nucleosome-binding domain 5 (HMGN5) in colorectal cancer tissues, to explore the function of HMGN5 on the proliferation and metastasis of colorectal cancer cells, and to further study the molecular mechanism of HMGN5 in the malignant progression of colorectal cancer (CRC). PATIENTS AND METHODS: The cancer tissues and para-carcinoma tissues were harvested from 40 patients with CRC. The expression of HMGN5 was detected via quantitative real-time polymerase chain reaction (qRT-PCR), and the relation between HMGN5 and clinical indexes of CRC patients was further analyzed. The CRC HT29 and HCT116 cell lines with high expression levels of HMGN5 were selected, and the HMGN5 knockdown model was established. The functions of HMGN5 on CRC cells were stated by cell counting kit-8 (CCK-8) assay and transwell migration assay. Then, the association between HMGN5 and fibroblast growth factor 12 (FGF12) was further explored via Dual-Luciferase reporter assay and reverse assay. RESULTS: The qRT-PCR showed that HMGN5 expression was significantly rising in cancer tissues compared to the control group. The incidence rate of lymph node metastasis and distant metastasis was higher in higher expression HMGN5 group than the lower expression HMGN5 group. The results of cell function experiments revealed that silence of HMGN5 could suppress the proliferation and migration of HT29 and HCT116. In addition, it was found using qRT-PCR that knockdown of HMGN5 could significantly down-regulate the expressions of FGF12, FGFR, PI3K and AKT in HT29 and HCT116 cells. The targeted binding relation between HMGN5 and FGF12 was also indicated by the dual-luciferase reporter assay. The consequence of qRT-PCR manifested that FGF12 expression markedly rose in CRC tissues, which had a positive correlation with HMGN5. Moreover, reverse assay indicated that the inhibitory effect of HMGN5 knockdown on the malignant progression of CRC could be reversed by recombinant FGF12, indicating once again that there is a mutual regulatory effect between HMGN5 and FGF12. CONCLUSIONS: HMGN5 can increase the proliferative and migrative capacity of CRC cells via targeted binding to FGF12. In addition, clinical data analyses demonstrate that HMGN5 is intimately related to the incidence rate of lymph node metastasis and distant metastasis in patients with CRC.

Prognostic value of HMGN family expression in acute myeloid leukemia.

Aim: The objective of this work was to investigate the prognostic role of the HMGN family in acute myeloid leukemia (AML). Methods: A total of 155 AML patients with HMGN1-5 expression data from the Cancer Genome Atlas database were enrolled in this study. Results: In the chemotherapy-only group, patients with high HMGN2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than those with low expression (all p < 0.05), whereas high HMGN5 expressers had shorter EFS and OS than the low expressers (all p < 0.05). Multivariate analysis identified that high HMGN2 expression was an independent favorable prognostic factor for patients who only received chemotherapy (all p < 0.05). HMGN family expression had no impact on EFS and OS in AML patients receiving allogeneic hematopoietic stem cell transplantation. Conclusion: High HMGN2/5 expression is a potential prognostic indicator for AML.

HMGN5 Silencing Suppresses Cell Biological Progression via AKT/MAPK Pathway in Human Glioblastoma Cells.

HMGN5 regulates biological function and molecular transcription via combining with a nucleosome. There has been growing evidence that aberrant expression of HMGN5 is associated with malignant neoplasm development and progression. In the present study, we found that the expression of HMGN5 is significantly higher in high-grade glioblastoma tissues than in low-grade samples. To clarify the function of HMGN5 in glioblastoma, we knocked down HMGN5 in U87 and U251 glioblastoma cells via siRNA. The results demonstrated that HMGN5 was involved in the regulation of proliferation and apoptosis, migration, and invasion of glioblastoma cells. These outcomes also indicated that silencing HMGN5 possibly suppressed the expression of p-AKT and p-ERK1/2. Taken together, our research reveals that HMGN5 might be an efficient target for glioblastoma-targeted therapy.

HMGN5 promotes IL-6-induced epithelial-mesenchymal transition of bladder cancer by interacting with Hsp27.

Bladder cancer (BC) is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes. High-mobility group nucleosome-binding domain 5 (HMGN5) is overexpressed in many cancers and could cause carcinogenesis in BC. By protein-protein-interaction (PPI) analysis, we found that heat shock protein 27 (Hsp27), also a crucial functional factor in BC carcinogenesis, is significantly related to HMGN5. Hsp27 is required for IL-6-mediated EMT via STAT3/Twist signaling in prostate cancer. Here, we hypothesize that HMGN5 may interact with Hsp27 to affect IL-6-induced EMT and invasion in BC via STAT3 signaling. In the present study, we found that HMGN5 and Hsp27 are highly expressed in BC tissues and positively correlated with each other. HMGN5 interacts with Hsp27 in vitro, to modulate the cell invasion and EMT in BC. Moreover, HMGN5 could modulate IL-6-Hsp27-induced EMT and invasion in BC cells by regulating STAT3 phosphorylation and STAT3 targeting of the Twist promoter. HMGN5 interacts with Hsp27 to promote tumor growth in a human BC xenograft model in nude mice. In summary, HMGN5 interacts with Hsp27 to promote IL-6-induced EMT, therefore promoting invasion in BC and contributing to the progression of BC.

Histone acetylation landscape in S. cerevisiae nhp6ab mutants reflects altered glucose metabolism.

BACKGROUND: The execution of many genetic programs, influenced by environmental conditions, is epigenetically controlled. Thus, small molecules of the intermediate metabolism being precursors of most of nutrition-deriving epigenetic modifications, sense the cell surrounding environment. METHODS: Here we describe histone H4K16 acetylation distribution in S. cerevisiae nhp6ab mutant, using ChIP-seq analysis; its transcription profile by RNA-seq and its metabolic features by studying the metabolome. We then intersected these three -omic approaches to unveil common crosspoints (if any). RESULTS: In the nhp6ab mutant, the glucose metabolism is switched to pathways leading to Acetyl-CoA synthesis. These enhanced pathways could lead to histone hyperacetylation altering RNA transcription, particularly of those metabolic genes that maintain high Acetyl-CoA availability. CONCLUSIONS: Thus, the absence of chromatin regulators like Nhp6 A and B, interferes with a regulative circular mechanism where histone modification, transcription and metabolism influence each other and contribute to clarify the more general phenomenon in which gene regulation feeds metabolic alterations on epigenetic basis. GENERAL SIGNIFICANCE: This study allowed us to identify, in these two factors, a common element of regulation in metabolism and chromatin acetylation state that could represent a powerful tool to find out relationships existing between metabolism and gene expression in more complex systems.

microRNA-183-3p Inhibits Progression of Human Prostate Cancer by Downregulating High-Mobility Group Nucleosome Binding Domain 5.

microRNAs are a class of noncoding RNAs that play important roles in cancer progression. microRNA-183-3p (miR-183-3p) is a novel microRNA that is dysregulated in many kinds of cancers. Our previous studies found high expression and oncologic role of high-mobility group nucleosome binding domain 5 (HMGN5) in prostate cancer. In this study, we found that miR-183-3p was downregulated in prostate cancer cells and primary tissues compared with normal controls. In addition, miR-183-3p expression was negatively correlated with HMGN5 expression. On the basis of bioinformatics predication and quantitative polymerase chain reaction and Western blot verification, it is demonstrated that miR-183-3p regulated HMGN5 expression. Luciferase reporter assay confirmed that miR-183-3p directly targeted the 3'-untranslated region of HMGN5. Interestingly, cell proliferation and migration inhibition and apoptosis induction were also observed in miR-183-3p transfected human prostate cancer VCap and C4-2 cells. Moreover, overexpression of HMGN5 significantly reversed the inhibitory effect on cell proliferation and migration and promoted effect on cell apoptosis by miR-183-3p. Our data suggest that dysfunction of miR-183-3p-HMGN5 axis plays an oncogenic role and can be a therapeutic target for prostate cancer.

Epigenetic regulation of REX1 expression and chromatin binding specificity by HMGNs.

HMGN proteins localize to chromatin regulatory sites and modulate the cell-type specific transcription profile; however, the molecular mechanism whereby these ubiquitous nucleosome binding proteins affect gene expression is not fully understood. Here, we show that HMGNs regulate the expression of Rex1, one of the most highly transcribed genes in mouse embryonic stem cells (ESCs), by recruiting the transcription factors NANOG, OCT4 and SOX2 to an ESC-specific super enhancer located in the 5' region of Rex1. HMGNs facilitate the establishment of an epigenetic landscape characteristic of active chromatin and enhancer promoter interactions, as seen by chromatin conformation capture. Loss of HMGNs alters the local epigenetic profile, increases histone H1 occupancy, decreases transcription factors binding and reduces enhancer promoter interactions, thereby downregulating, but not abolishing Rex1 expression. ChIP-seq analyses show high colocalization of HMGNs and of REX1, a zinc finger protein, at promoters and enhancers. Loss of HMGNs preferentially reduces the specific binding of REX1 to these chromatin regulatory sites. Thus, HMGNs affects both the expression and the chromatin binding specificity of REX1. We suggest that HMGNs affect cell-type specific gene expression by modulating the binding specificity of transcription factors to chromatin.

Hypoxia-Inducible Factor 1A Upregulates HMGN5 by Increasing the Expression of GATA1 and Plays a Role in Osteosarcoma Metastasis.

Osteosarcoma is one of the most common malignant tumors in children and adolescents and is characterized by early metastasis. High-mobility group N (HMGN) domains are involved in the development of several tumors. Our previous study found that HMGN5 is highly expressed in osteosarcoma tissues and knockdown of HMGN5 inhibits migration and invasion of U-2 OS and Saos-2 cells. A hypoxic environment is commonly found in solid tumors such as osteosarcoma and is likely to be associated with tumor metastasis, so we further explored the relationship between HMGN5 and the hypoxic environment. Hypoxia-inducible factor 1A (HIF1A) is an adaptive factor in the hypoxic environment. We found that HIF1A and HMGN5 were upregulated in osteosarcoma (OS) cells cultured in the hypoxic environment, and the results of overexpression and knockdown experiments showed that HIF1A upregulated the transcription factor GATA1 and further promoted the expression of HMGN5. In addition, MMP2 and MMP9 were subsequently upregulated through the c-jun pathway, and finally, this promoted the migration and invasion of OS cells. It is suggested that HMGN5 may be an important downstream factor for HIF1A to promote osteosarcoma metastasis. It has an important clinical significance for the selection of therapeutic targets for osteosarcoma.

Identification of novel biomarkers for hepatocellular carcinoma using transcriptome analysis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer in the world. To comprehensively investigate the utility of microRNAs (miRNAs) and protein-encoding transcripts (messenger RNAs [mRNAs]) in HCC as potential biomarkers for early detection and diagnosis, we exhaustively mined genomic data from three available omics datasets (GEO, Oncomine, and TCGA), analyzed the overlaps among gene expression studies from 920 hepatocellular carcinoma samples and 508 healthy (or adjacent normal) liver tissue samples available from six laboratories, and identified 178 differentially expressed genes (DEGs) associated with HCC. Paired with miRNA and lncRNA data, we identified 23 core genes that were targeted by nine differentially expressed miRNAs and 21 HCC-specific lncRNAs. We further demonstrated that alterations in these 23 genes were quite frequent, with five genes altered in over 5% of the population. Patients with high levels of YWHAZ, ENAH, and HMGN4 tended to have high-grade tumors and shorter overall survival, suggesting that these genes could be promising candidate biomarkers for disease and poor prognosis in patients with HCC. Our comprehensive mRNA, miRNA, and lncRNA omics analyses from multiple independent datasets identified robust molecules that may be used as biomarkers for early HCC detection and diagnosis.

HMGN5 expression in bladder cancer tissue and its role on prognosis.

OBJECTIVE: High mobility group protein N5 subtype (HMGN5) is overexpressed in bladder cancer tissue, while its specific mechanism in bladder cancer oncogenesis has not been fully elucidated. This study intends to investigate the impact of HMGN5 on clinical staging and prognosis of bladder cancer. PATIENTS AND METHODS: A total of 26 cases of patients with bladder transitional cell carcinoma (BTCC) received transurethral resection (TUR-BT) in our hospital between March 2015 and February 2016. Para-carcinoma tissue at 5 cm away from cancer tissue was selected as normal control. The expressions of HMGN5 mRNA and protein in different clinical stages were tested by Real-time PCR and Western blot. The relationship between HMGN5 expression and clinical stage along with prognosis was analyzed. RESULTS: HMGN5 mRNA was significantly elevated in BTCC tissue compared with that in para-carcinoma tissue (p < 0.05). HMGN5 mRNA level was gradually upregulated following BTCC upstage according to UICC-TNM stage and WHO stage. The level of HMGN5 protein showed similar changes with mRNA. Follow-up results demonstrated that patients with high HMGN5 level have more tendency of occurrence. CONCLUSIONS: HMGN5 protein level has an important influence on BTCC clinicopathological staging and prognosis. This investigation provides theoretical basis the future therapy of bladder cancer.

Silencing HMGN5 suppresses cell growth and promotes chemosensitivity in esophageal squamous cell carcinoma.

Previous study has demonstrated that high mobility group nucleosome-binding domain 5 (HMGN5) is involved in tumorigenesis and the development of multidrug resistance in several human cancers. However, the role of HMGN5 in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that HMGN5 was significantly upregulated in ESCC cells. Knockdown of HMGN5 significantly inhibited cell growth and induced cell apoptosis of ESCC cells. Moreover, knockdown of HMGN5 increased the sensitivity of ESCC cells towards cisplatin. By contrast, overexpression of HMGN5 showed the opposite effects. Further experiments demonstrated that HMGN5 regulated the expression of multidrug resistance 1, cyclin B1, and Bcl-2. Overall, our results reveal that HMGN5 promotes tumor progression of ESCC and is also an important regulator of chemoresistance. Our study suggests that inhibition of HMGN5 may be a potential strategy for improving effectiveness of ESCC treatment.