In Silico Analysis of Functional SNPs in Genes of Complete Androgen Insensitivity Syndrome (CAIS): A Retrospective, Case-Control Study.

Background: Complete androgen insensitivity syndrome (CAIS) is one of the categories of androgen insensitivity syndrome (AIS) described as complete failure of the cell to react to androgens with external genitalia of a normal female. People with AIS condition are genetically male, with XY karyotype in each cell, but their bodies are unable to respond to male sex hormones (called androgens). It is associated with infertility as well as developing cancerous conditions. The genetic association of CAIS involves polymorphism of genes such as NR5A1, SOX9, SRD5A2, CBX2, GATA4, and SRY. Their mutation and participation in genetics of CAIS can be studied by Single Nucleotide polymorphism (SNP) analysis which is a way to detect genetic variations. SNP in coding region leads to synonymous and non-synonymous mutations. Hence, this study highlights analysis of SNPs associated with CAIS. Our aim is to study SNP analysis of NR5A1, SOX9, SRD5A2, CBX2, GATA4, SRY genes in Complete Androgen Insensitivity Syndrome. Methods: SIFT and Polyphen analysis was performed for all the genes and samples were subjected for PCR-SSCP technique. Results: SNPs were analyzed for the genes associated with CAIS. Benign and damaging SNPs were identified. DNA Samples were amplified using PCR technique and they will be analyzed using Single-strand conformation polymorphism (SSCP). Conclusions: As SNPs have decreased stability, damaging and benign character, they can be used as candidate hallmarks in study of Complete Androgen Insensitivity Syndrome.

CBX2 Deletion Suppresses Growth and Metastasis of Colorectal Cancer by Mettl3-p38/ERK MAPK Signalling Pathway.

Colorectal cancer (CRC) seriously endangers human health owing to its high morbidity and mortality. Previous studies have suggested that high expression of CBX2 may be associated with poor prognosis in CRC patients. However, its functional role in CRC remains to be elucidated. Herein, we found that CBX2 overexpression in colorectal cancer tissue compared with adjacent tissues. Additionally, forest maps and the nomogram model indicated that elevated CBX2 expression was an independent prognostic factor in CRC. Moreover, we confirmed that the deletion of CBX2 markedly suppressed the proliferation and migration of CRC cells in vitro and in vivo. Furthermore, downregulation of CBX2 promotes CRC cell apoptosis and hinders the cell cycle. Mechanistically, our data demonstrated that deletion of CBX2 inhibited the MAPK signaling pathway by regulating the protein levels of Mettl3. In conclusion, our study demonstrated that CBX2 is a vital tumor suppressor in CRC and could be a promising anti-cancer therapeutic target.

Sparse CBX2 nucleates many Polycomb proteins to promote facultative heterochromatinization of Polycomb target genes.

Facultative heterochromatinization of genomic regulators by Polycomb repressive complex (PRC) 1 and 2 is essential in development and differentiation; however, the underlying molecular mechanisms remain obscure. Using genetic engineering, molecular approaches, and live-cell single-molecule imaging, we quantify the number of proteins within condensates formed through liquid-liquid phase separation (LLPS) and find that in mouse embryonic stem cells (mESCs), approximately 3 CBX2 proteins nucleate many PRC1 and PRC2 subunits to form one non-stoichiometric condensate. We demonstrate that sparse CBX2 prevents Polycomb proteins from migrating to constitutive heterochromatin, demarcates the spatial boundaries of facultative heterochromatin, controls the deposition of H3K27me3, regulates transcription, and impacts cellular differentiation. Furthermore, we show that LLPS of CBX2 is required for the demarcation and deposition of H3K27me3 and is essential for cellular differentiation. Our findings uncover new functional roles of LLPS in the formation of facultative heterochromatin and unravel a new mechanism by which low-abundant proteins nucleate many other proteins to form compartments that enable them to execute their functions.

Subcellular expression pattern and clinical significance of CBX2 and CBX7 in breast cancer subtypes.

Chromobox (CBX)2 and CBX7, members of CBX family protein, show diverse expression patterns and contrasting roles in certain cancers. We aimed to investigate the subcellular expression patterns and clinical significances of CBXs in breast cancer (BC) subtypes, which have heterogeneous clinical course and therapeutic responses. Among the subtypes, the triple-negative BC (TNBC) is a heterogeneous group that lacks specific markers. We categorized TNBC into quadruple-negative BC (QNBC) and TNBC, based on androgen receptor (AR) status, to make the groups more homogeneous. Immunohistochemistry for CBX proteins was performed on 323 primary invasive BC tissues and their clinical significances were analyzed. Cytoplasmic CBX2 (CBX2-c) was linked to adverse clinicopathological factors and TNBC and QNBC subtypes. In contrast, nuclear CBX7 (CBX7-n) was associated with favorable parameters and luminal A subtype. CBX2-c expression increased progressively from that in benign lesions to that in in situ carcinomas and invasive cancers, whereas CBX7-n and AR expressions showed sequential downregulation. AR was lower in metastatic tissues compared to matched primary cancer tissues. We speculate that the upregulation of CBX2-c and downregulation of CBX7-n could play a role in breast oncogenesis and an adverse clinical course, suggesting them as potential prognostic markers and therapeutic targets in invasive BCs.

Prognostic hub gene CBX2 drives a cancer stem cell-like phenotype in HCC revealed by multi-omics and multi-cohorts.

Hepatocellular carcinoma (HCC) is a malignant tumor with a high prevalence and fatality rate. CBX2 has been demonstrated to impact the development and advancement of various cancers, albeit it has received limited attention in relation to HCC. In this study, CBX2 and CEP55 were screened out with the refined triple regulatory networks constructed by total RNA-seq datasets (TCGA-LIHC, GSE140845) and a robust prognostic model. Aberrantly higher expression levels of CBX2 and CEP55 in HCC may be caused by CNV alterations, promoter hypo-methylation, open chromatin accessibility, and greater active marks such as H3K4me3, H3K4me1, and H3K27ac. Functionally, CBX2, which was highly correlated with CD44, shaped a cancer stem cell-like phenotype by positively regulating cell-cycle progression, proliferation, invasion, metastasis, wound healing, and radiation resistance, revealed by combining bulk RNA-seq and scRNA-seq datasets. CBX2 knockdown validated its role in affecting the cell cycle. Importantly, we revealed CBX2 could activate gene by cooperating with co-regulators or not rather than a recognizer of the repressive mark H3K27me3. For instance, we uncovered CBX2 bound to promoter of CTNNB1 and CEP55 to augment their expressions. CBX2 showed a highly positive correlation with CEP55 at pan-cancer level. In addition, CBX2 and CEP55 may enhance extracellular matrix reprograming via cancer-associated fibroblast. Surprisingly, patients with high expression of CBX2 or CEP55 exhibited a higher response to immunotherapy, indicating that CBX2 and CEP55 may be promising therapeutic targets for HCC patients.

Cancer-associated fibroblasts secret extracellular vesicles to support cell proliferation and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma.

As the critical components of tumor microenvironment, cancer-associated fibroblasts (CAFs) support the development of various type of cancers, including laryngeal squamous cell carcinoma (LSCC), but the detailed molecular mechanisms by which cancer-associated fibroblasts interact with LSCC cells to facilitate its progression have not been fully uncovered. In the present study, by analyzing the contents from normal fibroblasts (NFs) and cancer-associated fibroblasts-derived extracellular vesicles (EVs) with Real-Time qPCR analysis, we found that the tumor-initiating LncRNA TUC338 was significantly upregulated in the cancer-associated fibroblasts-derived extracellular vesicles, compared to the normal fibroblasts-secreted extracellular vesicles. Further experiments confirmed that cancer-associated fibroblasts-derived extracellular vesicles promoted cell proliferation, colony formation abilities, epithelial-mesenchymal transition (EMT) and tumorigenesis of LSCC cells via delivering LncRNA TUC338. The mechanical experiments verified that LncRNA TUC338 was stabilized by METTL3/YTHDF1-mediated N6-methyladenosine (m6A) modifications, and elevated LncRNA TUC338 sponged miR-8485 to upregulate chromobox homolog 2 (CBX2) in LSCC cells in a competing endogenous RNA mechanisms-dependent manner. Moreover, our rescue experiments evidenced that cancer-associated fibroblasts-derived LncRNA TUC338-containing extracellular vesicles-induced supportive effects in LSCC aggressiveness were all abrogated by overexpressing miR-8485 and silencing CBX2. Collectively, this study is the first to identify a novel m6A/LncRNA TUC338/miR-8485/CBX2 axis in CAFs-EVs-mediated LSCC development, and to show its potential as a diagnostic biomarker for LSCC.

MiR-30a-5p inhibits cell behaviors in esophageal cancer via modulating CBX2.

BACKGROUND: This investigation studied the impacts of the miR-30a-5p/CBX2 axis on esophageal cancer (EC). METHODS: Research objects were ascertained using The Cancer Genome Atlas database. Followed by qRT-PCR, western blot, dual-luciferase reporter, MTT, Transwell, and wound healing approaches, we tested gene expression and varying cell behaviors RESULTS: Conspicuously miR-30 family members (miR-30a-5p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-30e-5p) downregulation and CBX2 upregulation were discovered in EC cells. miR-30 family members target CBX2 and inhibited CBX2 expression. EC cell behaviors were inhibited by miR-30a-5p/CBX2 axis. CONCLUSION: MiR-30a-5p draws a new inspiration for EC treatment.

PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1.

Polycomb repressive complex 2 (PRC2) mediates H3K27me3 deposition, which is thought to recruit canonical PRC1 (cPRC1) via chromodomain-containing CBX proteins to promote stable repression of developmental genes. PRC2 forms two major subcomplexes, PRC2.1 and PRC2.2, but their specific roles remain unclear. Through genetic knockout (KO) and replacement of PRC2 subcomplex-specific subunits in naïve and primed pluripotent cells, we uncover distinct roles for PRC2.1 and PRC2.2 in mediating the recruitment of different forms of cPRC1. PRC2.1 catalyzes the majority of H3K27me3 at Polycomb target genes and is sufficient to promote recruitment of CBX2/4-cPRC1 but not CBX7-cPRC1. Conversely, while PRC2.2 is poor at catalyzing H3K27me3, we find that its accessory protein JARID2 is essential for recruitment of CBX7-cPRC1 and the consequent 3D chromatin interactions at Polycomb target genes. We therefore define distinct contributions of PRC2.1- and PRC2.2-specific accessory proteins to Polycomb-mediated repression and uncover a new mechanism for cPRC1 recruitment.

Epigenetics-based diagnostic and therapeutic strategies: shifting the paradigm in prostate cancer.

Despite recent advances, prostate cancer (PCa) remains a leading cause of cancer morbidity and mortality. Clinically, PCa screening methods display low sensitivity and specificity, leading to suboptimal patient care. Recent research suggests that PCa progression is regulated by a coordinated spectrum of epigenetic alterations that notably involves noncoding RNAs. These molecular aberrations drive PCa progression by inducing gene expression programs that promote metastatic dissemination. Epigenetic proteins and noncoding RNAs can be detected noninvasively in body fluids, allowing improved PCa screening and prognosis. In addition, epigenetic alterations can be targeted pharmacologically, providing unprecedented therapeutic opportunities. This work reviews the current literature linking epigenetic dysregulation and PCa progression and proposes a framework for integrating epigenetic strategies into the clinical management of PCa.

CBX2-mediated suppression of SIAH2 triggers WNK1 accumulations to promote glycolysis in hepatocellular carcinoma.

Previous studies have highlighted the poor prognosis of liver cancer, and treatment effects are overall limited. We aimed to confirm the biological roles of SIAH2 in liver cancer and provide potential therapeutic targets. Differential analysis was conducted based on public datasets and found that SIAH2 expressed lowly in HCC samples relative to normal tissues, which was demonstrated in tumor samples via immunohistochemistry (IHC). Besides, SIAH2 overexpression could significantly suppress HCC proliferation. SIAH2 deficiency induced cell proliferation, migration and self-renewal abilities in vitro and in vivo. Mechanistically, SIAH2 could interact with WNK1, and trigger the ubiquitination and degradation of WNK1 proteins. In addition, low SIAH2 depended on elevated WNK1 proteins to drive HCC malignant features, including proliferation, migration and stemness. Meanwhile, we further found that CBX2 could regulate SIAH2 expressions. CBX2 cooperated with EZH2 to mediate the H3K27me3 enrichment on the promoter region of SIAH2 to suppress its transcriptional levels. High CBX2/EZH2 levels in HCC correlated with poor prognosis of patients. Gene set enrichment analysis (GSEA) further implicated that WNK1 correlates tightly with glycolytic process in HCC samples. WNK1 overexpression was found to notably enhance glycolytic activity, whereas WNK1 deficiency could significantly suppress the HCC glycolysis activity. Lastly, the subcutaneous tumor model further demonstrated that targeting WNK1 was effective to inhibit the in vivo tumor growth of SIAH2low HCC. Collectively, down-regulated SIAH2 expressions induced by CBX2/EZH2 could drive progression and glycolysis via accumulating WNK1 proteins, indicating that CBX2/SIAH2/WNK1 axis is a potential prognostic biomarker and therapeutic vulnerability for human HCC.

Loss of CBX2 causes genomic instability and Wnt activation in high grade serous ovarian carcinoma cells.

High grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis-associated PRC1 components were identified through data-mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3. Complete loss of CBX2 by CRISPR-cas9 editing (CBX2KO ) destabilized genome stability with increased spontaneous chromosomal breaks and tendency to polyploidy accompanied by disrupted cell cycle especially stalled G2/M transition and caused severe cell death. Wnt/ß-catenin/LEF1/TCF7L1 was activated in surviving OVCAR4-CBX2KO clones to bypass the crisis caused by loss of CBX2. The relieve of TCF7L1 core-promoter region occupied by CBX2 might be one of the possible explanations to TCF7L1 increase in OVCAR4-CBX2KO clones. Subcutaneous tumor model further validated that depletion of CBX2 repressed HGSOC cell line derived tumor growth. High immunohistochemistry score of CBX2 in primary ovarian cancer tissue associated with advanced clinical stage (p = 0.033), poor overall survival (HR = 3.056, 95% CI: 1.024-9.123), and progression free survival (HR = 4.455, 95% CI: 1.513-13.118) in HGSOC. Overall, our results suggested that CBX2 was a promising prognostic factor and therapeutic target in HGSOC.

cbx2 is a functional target of the let-7 family in the gonad of Japanese flounder (Paralichthys olivaceus).

As a key member of the miRNA family, the role and target gene of the let-7 family in the gonad of Japanese flounder (Paralichthys olivaceus) is unclear. Chromobox homolog 2 (CBX2) is one of the core components of the polycomb group complex (PcG) and significantly influences gonadal development. The deletion of CBX2 can lead to sex reversal in mammals. Therefore, exploring the relationship between the let-7 family and cbx2 is crucial to clarify the role played by the let-7 family in the gonad of Japanese flounder. We predicted and verified the target interaction between the let-7 family and cbx2. The results showed that cbx2 was a direct target of let-7d, let-7e, let-7g, let-7j, and let-7b. Among them, let-7d, let-7e, let-7g, and let-7j exhibited an extremely significant targeting relationship with cbx2 (p < 0.001). Taking let-7g as an example, we further investigated the regulatory role between let-7g and cbx2 in the gonad by miRNA overexpression and inhibition experiments in primary testis cells. The results revealed that let-7g could negatively regulate cbx2 at the level of primary testis cells. And the expression of sf1 (steroidogenic factor 1) was also significantly decreased after the interference of cbx2 siRNA. This suggests that the let-7 family may be involved in the Japanese flounder gonadal development via targeting cbx2.

The Epigenetic Regulatory Protein CBX2 Promotes mTORC1 Signalling and Inhibits DREAM Complex Activity to Drive Breast Cancer Cell Growth.

Chromobox 2 (CBX2) is a chromatin-binding component of polycomb repressive complex 1, which causes gene silencing. CBX2 expression is elevated in triple-negative breast cancer (TNBC), for which there are few therapeutic options. Here, we aimed to investigate the functional role of CBX2 in TNBC. CBX2 knockdown in TNBC models reduced cell numbers, which was rescued by ectopic expression of wild-type CBX2 but not a chromatin binding-deficient mutant. Blocking CBX2 chromatin interactions using the inhibitor SW2_152F also reduced cell growth, suggesting CBX2 chromatin binding is crucial for TNBC progression. RNA sequencing and gene set enrichment analysis of CBX2-depleted cells identified downregulation of oncogenic signalling pathways, including mTORC1 and E2F signalling. Subsequent analysis identified that CBX2 represses the expression of mTORC1 inhibitors and the tumour suppressor RBL2. RBL2 repression, in turn, inhibits DREAM complex activity. The DREAM complex inhibits E2F signalling, causing cell senescence; therefore, inhibition of the DREAM complex via CBX2 may be a key oncogenic driver. We observed similar effects in oestrogen receptor-positive breast cancer, and analysis of patient datasets suggested CBX2 inhibits RBL2 activity in other cancer types. Therapeutic inhibition of CBX2 could therefore repress mTORC1 activation and promote DREAM complex-mediated senescence in TNBC and could have similar effects in other cancer types.

CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway.

BACKGROUND: The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival. However, its role in leukemia is still unclear. METHODS: We exploited reverse genetic approaches to investigate the role of CBX2 in human leukemic cell lines and ex vivo samples. We also analyzed phenotypic effects following CBX2 silencing using cellular and molecular assays and related functional mechanisms by ATAC-seq and RNA-seq. We then performed bioinformatic analysis of ChIP-seq data to explore the influence of histone modifications in CBX2-mediated open chromatin sites. Lastly, we used molecular assays to determine the contribution of CBX2-regulated pathways to leukemic phenotype. RESULTS: We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34+ cells. Decreased CBX2 RNA levels prompted a robust reduction in cell proliferation and induction of apoptosis. Similarly, sensitivity to CBX2 silencing was observed in primary acute myeloid leukemia samples. CBX2 suppression increased genome-wide chromatin accessibility followed by alteration of leukemic cell transcriptional programs, resulting in enrichment of cell death pathways and downregulation of survival genes. Intriguingly, CBX2 silencing induced epigenetic reprogramming at p38 MAPK-associated regulatory sites with consequent deregulation of gene expression. CONCLUSIONS: Our results identify CBX2 as a crucial player in leukemia progression and highlight a potential druggable CBX2-p38 MAPK network in AML.

Cannabidiol promotes apoptosis of osteosarcoma cells in vitro and in vivo by activating the SP1-CBX2 axis.

Osteosarcoma is the most common primary malignant bone tumor that often occurs in children, adolescents, and young adults. Cannabidiol plays an essential role in cancer treatment. However, its effects on osteosarcoma have not yet been addressed. In the present study, we investigated the pharmacological effects of cannabidiol on osteosarcoma. We found that cannabidiol effectively suppressed the proliferation and colony formation of osteosarcoma cells. Further studies showed that cannabidiol significantly promoted cell apoptosis and changes in cell apoptosis-related gene proteins in vitro. In addition, cannabidiol administration inhibited tumor growth and promoted the apoptosis of osteosarcoma cells in a mouse xenograft model. The in vitro study also demonstrated that SP1 contributes to chromobox protein homolog 2 (CBX2) reduction in cannabidiol-treated MG63 and HOS cells, and that cannabidiol may recruit SP1 into the CBX2 promoter regions to downregulate CBX2 expression at the transcriptional level and promote osteosarcoma cell apoptosis. Further, the result showed that cannabidiol suppressed osteosarcoma cell migration. In summary, cannabidiol effectively promoted the apoptosis of osteosarcoma cells in vitro and in vivo and suppressed tumor growth in a mouse xenograft model by regulating the SP1-CBX2 axis. This finding provides novel therapeutic strategies for osteosarcoma in the clinic.

CBX2 in DSD: The Quirky Kid on the Block.

Sex development is an intricate and crucial process in all vertebrates that ensures the continued propagation of genetic diversity within a species, and ultimately their survival. Perturbations in this process can manifest as disorders/differences of sex development (DSD). Various transcriptional networks have been linked to development of the gonad into either male or female, which is actively driven by a set of genes that function in a juxtaposed manner and is maintained through the developmental stages to preserve the final sexual identity. One such identified gene is Chromobox homolog 2 (CBX2), an important ortholog of the Polycomb group (PcG) proteins, that functions as both chromatin modifier and highly dynamic transactivator. CBX2 was shown to be an essential factor for gonadal development in mammals, as genetic variants or loss-of-function of CBX2 can cause sex reversal in mice and humans. Here we will provide an overview of CBX2, its biological functions at molecular level, and the CBX2-dependent transcriptional landscape in gonadal development and DSD.

CBX2 and EZH2 cooperatively promote the growth and metastasis of lung adenocarcinoma.

The disruption of epigenetic regulation is common in tumors; the abnormal expression of epigenetic factors leads to cancer occurrence and development. In this study, to investigate the potential function of histone methylation regulators in lung adenocarcinoma (LUAD), we performed differential expression analysis using RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) database, and identified CBX2 and EZH2 as obviously upregulated histone methylation regulators. CBX2 knockdown significantly inhibited LUAD cell growth and metastasis in vitro and in vivo. The combined high expression of CBX2 and EZH2 was an indicator of poor prognosis in LUAD. The inhibition of both CBX2 and EZH2 exerted cooperative suppressive effects on the growth and metastasis of LUAD cells. Mechanistically, we revealed that CBX2 and EZH2 downregulated several PPAR signaling pathway genes and tumor suppressor genes through binding to their promoter cooperatively or separately. Furthermore, knockdown of CBX2 improved the therapeutic efficiency of EZH2 inhibitor on A549 cells. Our study reveals the cooperative oncogenic role of CBX2 and EZH2 in promoting LUAD progression, thereby providing potential targets for LUAD diagnosis and therapy.

Circ_0061140 knockdown inhibits tumorigenesis and improves PTX sensitivity by regulating miR-136/CBX2 axis in ovarian cancer.

BACKGROUND: Ovarian cancer is an aggressive tumor in women with high mortality. Paclitaxel (PTX) can be used for the chemotherapy of ovarian cancer. Here, the roles of circular_0061140 (circ_0061140) in PTX sensitivity and malignant progression of ovarian cancer are unveiled. METHODS: The expressions of circ_0061140, microRNA-136 (miR-136) and chromobox 2 (CBX2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot. The half maximal inhibitory concentration (IC50) of PTX was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was investigated by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by transwell assay. The binding relationship between miR-136 and circ_0061140 or CBX2 was predicted by interactome or starbase online database, and identified by dual-luciferase reporter assay. The effects of circ_0061140 on tumor formation and PTX sensitivity in vivo were disclosed by tumor formation assay. RESULTS: Circ_0061140 and CBX2 expressions were upregulated, while miR-136 expression was downregulated in PTX-resistant tissues and cells compared with control groups. Circ_0061140 knockdown repressed cell proliferation, migration and invasion, and promoted cell apoptosis and PTX sensitivity; however, these effects were restrained by miR-136 RNAi. Additionally, circ_0061140 was a sponge of miR-136, and miR-136 bound to CBX2. Furthermore, circ_0061140 knockdown inhibited tumor formation and improved PTX sensitivity in vivo. CONCLUSIONS: Circ_0061140 silencing repressed the progression and PTX resistance of ovarian cancer by downregulating CBX2 expression via sponging miR-136, which provided novel insight into studying the therapy of ovarian cancer with PTX.

CBX2 Induces Glioma Cell Proliferation and Invasion Through the Akt/PI3K Pathway.

Glioma is the most common primary intracranial tumor. Abnormal expression of CBX2 (ChromoBox2) is associated with tumorigenesis and tumor development. TCGA data in UALCAN showed that CBX2 was overexpressed in glioma tissue. To confirm the role of CBX2 in glioma, we regulated the level of CBX2 and conducted colony formation, Transwell, and CCK-8 assays to verify the effect of CBX2. The results showed that CBX2 knockdown reduced glioma cell proliferation and invasion and that the cells were less tumorigenic. CBX2 overexpression induced glioma cell proliferation and invasion and glioma stem cell self-renewal. The animal experiments showed that CBX2 knockdown inhibited glioma growth and improved survival time. CBX2 knockdown inhibited activation of the Akt/PI3K pathway. epidermal growth factor rescued the effects of CBX2. CBX2 could induce the growth and invasion of glioma cells via the Akt/PI3K pathway.

M33 condenses chromatin through nuclear body formation and methylation of both histone H3 lysine 9 and lysine 27.

Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases.