Search Results (10)

Canopy FGF signaling regulator 3 (CNPY3) is a cochaperone of the molecular chaperone GRP94. CNPY3 is critical for the post-translational maturation of toll-like receptors and for regulating inflammasome signaling. However, the role of CNPY3 in cancer development and progression is still not fully understood. In this study, we aimed to investigate the role of CNPY3 in human breast cancer progression and metastasis. We used genomic and clinical information from multiple databases to profile CNPY3 and GRP94 in human cancers. We found that CNPY3 and GRP94 were elevated in human breast cancers compared to normal tissue. Higher expression of CNPY3 correlated with cancer progression and poor clinical outcomes in breast cancers. We confirmed these findings using a human breast cancer tissue array. We silenced CNPY3 in human breast cancer cells using a CRISPR/Cas9 system. For the first time, we found that deletion of CNPY3 significantly reduced tumor growth and metastasis in vitro and in vivo. Additionally, network and enrichment analyses revealed that changes in the unfolded protein response pathway and immune-related genes were significantly dependent on alterations in CNPY3 and GRP94. This study suggests that CNPY3 is a potential biomarker and novel therapeutic target for cancers. Full article

Canopy FGF signaling regulator 2 (CNPY2) has emerged as a crucial player in cancer development by promoting cell proliferation, tissue repair, and angiogenesis. This review synthesizes the current understanding of CNPY2’s role in solid tumors, particularly renal cell carcinoma, prostate cancer, hepatocellular carcinoma, and non-small-cell lung cancer. CNPY2 modulates key pathways such as p53, MYLIP, NF-κB, and AKT/GSK3β, thereby driving tumor growth and progression. In renal cell carcinoma, CNPY2 paradoxically promotes tumor growth through p53 upregulation, while in hepatocellular carcinoma, CNPY2 drives cell cycle progression via p53 destabilization. In prostate cancer, it enhances tumor progression by stabilizing androgen receptors through MYLIP interaction, and in non-small-cell lung cancer, it contributes to chemoresistance and metastasis through NF-κB and AKT/GSK3β signaling. Additionally, CNPY2 influences the tumor microenvironment, impacting immune function and metastatic potential. As a potential biomarker, CNPY2 shows promise for cancer detection and prognosis, particularly when used in combination with other markers. Early therapeutic strategies, including siRNA and miRNA approaches, are under exploration, though challenges remain due to CNPY2’s expression in normal tissues and potential off-target effects. This review underscores the need for further research to fully elucidate CNPY2’s oncogenic mechanisms and develop targeted therapies. Improved understanding of CNPY2’s diverse roles may lead to novel diagnostic and therapeutic approaches in solid tumors. Full article

Two new metal–organic multi-component compounds of Ni(II) and Co(II), viz. [Ni(3-CNpy)₂(H₂O)₄]ADS·2.75H₂O (1) and [Co(3-CNpy)₂(H₂O)₄](4-ClbzSO₃)₂ (2) (3-CNpy = 3-cyanopyridine, ADS = anthraquinone-1,5-disulfonate, 4-ClbzSO₃ = 4-chlorobenzenesulfonate), were synthesized and characterized using single crystal XRD, TGA, spectroscopic (IR, electronic) and elemental analyses. Both the compounds crystallize as multi-component compounds of Ni(II) and Co(II), with uncoordinated ADS and 4-ClbzSO₃ moieties in the crystal lattice, respectively. Crystal structure analyses revealed the presence of antiparallel nitrile···nitrile and π-stacked assemblies involving alternate coordinated 3-CNpy and uncoordinated ADS and 4-ClbzSO₃ moieties. Moreover, unconventional charge reverse Cl∙∙∙N halogen bonding contacts observed in compound 2 provide additional reinforcement to the crystal structure. Theoretical calculations confirm that the H-bonding interactions, along with anion–π(arene) and anion–π(CN) in 1 and π–π, antiparallel CN···CN and charge reverse Cl···N halogen bonds in 2, play crucial roles in the solid state stability of the compounds. In vitro anticancer activities observed through the trypan blue cell cytotoxicity assay reveal that the compounds induce significant concentration dependent cytotoxicity in Dalton’s lymphoma (DL) cancer cells, with nominal effects in normal healthy cells. Molecular docking studies reveal that the compounds can effectively bind with the active sites of anti-apoptotic proteins, which are actively involved in cancer progression. Full article

While studying myoblast methylomes and transcriptomes, we found that CDH15 had a remarkable preference for expression in both myoblasts and cerebellum. To understand how widespread such a relationship was and its epigenetic and biological correlates, we systematically looked for genes with similar transcription profiles and analyzed their DNA methylation and chromatin state and accessibility profiles in many different cell populations. Twenty genes were expressed preferentially in myoblasts and cerebellum (Myob/Cbl genes). Some shared DNA hypo- or hypermethylated regions in myoblasts and cerebellum. Particularly striking was ZNF556, whose promoter is hypomethylated in expressing cells but highly methylated in the many cell populations that do not express the gene. In reporter gene assays, we demonstrated that its promoter’s activity is methylation sensitive. The atypical epigenetics of ZNF556 may have originated from its promoter’s hypomethylation and selective activation in sperm progenitors and oocytes. Five of the Myob/Cbl genes (KCNJ12, ST8SIA5, ZIC1, VAX2, and EN2) have much higher RNA levels in cerebellum than in myoblasts and displayed myoblast-specific hypermethylation upstream and/or downstream of their promoters that may downmodulate expression. Differential DNA methylation was associated with alternative promoter usage for Myob/Cbl genes MCF2L, DOK7, CNPY1, and ANK1. Myob/Cbl genes PAX3, LBX1, ZNF556, ZIC1, EN2, and VAX2 encode sequence-specific transcription factors, which likely help drive the myoblast and cerebellum specificity of other Myob/Cbl genes. This study extends our understanding of epigenetic/transcription associations related to differentiation and may help elucidate relationships between epigenetic signatures and muscular dystrophies or cerebellar-linked neuropathologies. Full article

The present study was aimed at identifying novel proteins in endometrial cancer (EC), employing proteomic analysis of tissues obtained after surgery. A differential MS-based proteomic analysis was conducted from whole tissues dissected from biopsies from post-menopausal women, histologically confirmed as endometrial cancer (two endometrioid and two serous; n = 4) or normal atrophic endometrium (n = 4), providing 888 differentially expressed proteins with 246 of these previously documented elsewhere as expressed in EC and 372 proteins not previously demonstrated to be expressed in EC but associated with other types of cancer. Additionally, 33 proteins not recorded previously in PubMed as being expressed in any forms of cancer were also identified, with only 26 of these proteins having a publication associated with their expression patterns or putative functions. The putative functions of the 26 proteins (GRN, APP, HEXA, CST3, CAD, QARS, SIAE, WARS, MYH8, CLTB, GOLIM4, SCARB2, BOD1L1, C14orf142, C9orf142, CCDC13, CNPY4, FAM169A, HN1L, PIGT, PLCL1, PMFBP1, SARS2, SCPEP1, SLC25A24 and ZC3H4) in other tissues point towards and provide a basis for further investigation of these previously unrecognised novel EC proteins. The developmental biology, disease, extracellular matrix, homeostatic, immune, metabolic (both RNA and protein), programmed cell death, signal transduction, molecular transport, transcriptional networks and as yet uncharacterised pathways indicate that these proteins are potentially involved in endometrial carcinogenesis and thus may be important in EC diagnosis, prognostication and treatment and thus are worthy of further investigation. Full article

Cancers of the urinary tract are one of the most common malignancies worldwide, causing high morbidity and mortality, and representing a social burden. Upper tract urothelial carcinoma (UTUC) accounts for 5–10% of urinary tract cancers, and its oncogenic mechanisms remain elusive. We postulated that cancers of the lower and the upper urinary tract may share some important oncogenic mechanisms. Therefore, the oncogenic mechanisms discovered in the lower urinary tract may guide the investigation of molecular mechanisms in the upper urinary tract. Based on this strategy, we revisited a high-quality transcriptome dataset of 510 patients with non-muscle invasive bladder cancer (NMIBC), and performed an innovative gene set enrichment analysis of the transcriptome. We discovered that the epigenetic regulation of polycomb repressive complex 2 (PRC2) is responsible for the recurrence and progression of lower-track urinary cancers. Additionally, a PRC2-related gene signature model was discovered to be effective in classifying bladder cancer patients with distinct susceptibility of subsequent recurrence and progression (log-rank p < 0.001 and = 0.001, respectively). We continued to discover that the same model can differentiate stage T3 UTUC patients from stage Ta/T1 patients (p = 0.026). Immunohistochemical staining revealed the presence of PRC2 components (EZH2, EED, and SUZ12) and methylated PRC2 substrates (H3K27me3) in the archived UTUC tissues. The H3K27me3 exhibited higher intensity and area intensity product in stage T3 UTUC tissues than in stage Ta/T1 tissues (p = 0.006 and 0.015, respectively), implicating stronger PRC2 activity in advanced UTUC. The relationship between H3K27 methylation and gene expression is examined using correlations. The H3K27me3 abundance is positively correlated with the expression levels of CDC26, RP11-2B6, MAPK1IP1L, SFR1, RP11-196B3, CDK5RAP2, ANXA5, STX11, PSMD5, and FGFRL1. It is also negatively correlated with CNPY2, KB-1208A12, RP11-175B9, ZNF692, RANP8, RP11-245C17, TMEM266, FBXW9, SUGT1P2, and PRH1. In conclusion, PRC2 and its epigenetic effects are major oncogenic mechanisms underlying both bladder cancer and UTUC. The epigenetically regulated genes of PRC2 in urothelial carcinoma were also elucidated using correlation statistics. Full article

Four co-crystals involving dicarboxylic acids and pyridine derivatives, viz. (ox)_0.5(2-CNpy) (1), (adp)(4-CNpy)₂ (2), (tp)(4-CNpy)₂ (3) and (adp)(3-CNpy)₂ (4) (ox = oxalic acid, tp = terephthalic acid, adp = adipic acid, CNpy = cyanopyridine), have been synthesized at room temperature in water medium. Crystal-structure analysis of co-crystal 1 reveals the presence of unconventional O···π(oxalic acid)-hole interaction with the C-C bond of ox moiety, along with parallel nitrile–nitrile interactions. The structural topologies of co-crystals 2–4 unfold the presence of antiparallel nitrile–nitrile interactions involving the CNpy moieties. The molecular associations involving the H-bonds and other unconventional contacts among the co-formers of the multicomponent co-crystals are analyzed using density functional theory (DFT) calculations combined with molecular electrostatic potential (MEP) surface, quantum theory of atoms-in-molecules (QTAIM) and noncovalent interaction (NCI) plot computational tools. The computational studies revealed the presence of unconventional O···π-hole interaction in 1 and the H-bonded synthons with π-stacked nitrile contacts involving CNpy moieties in co-crystals 2–4. The energetic features of the noncovalent contacts reveal the crucial roles of the H-bonding synthons and π-stacking interactions in the multicomponent compounds. Full article

In the present study, the role of a novel protein involved in neurite development and endoplasmic reticulum (ER) stress, canopy homolog 2 (CNPY2), was investigated in mouse and human hepatocarcinogenesis. Firstly, a sensitive quantitative and qualitative detection of protein expression using QSTAR Elite LC-Ms/Ms was performed for the analysis of lysates of microdissected hepatocellular altered foci (AF), adenomas (HCAs), carcinomas (HCCs) and peri-tumoral livers from C57Bl/6J mice treated with diethylnitrosamine (DEN) and then maintained for 27 or 38 weeks on basal diet. Significant overexpression of 18.5 kDa CNPY2 processed form was demonstrated in AF, HCAs and HCCs, while low expression was observed in the livers of DEN-treated and control mice. Furthermore, CNPY2 elevation in AF and tumors was coordinated with accumulation of numerous cytoskeletal proteins, including cytokeratins 8 and 18, actin, non-muscle myosin and septin 9 and those involved in ER and mitochondrial stresses such as calreticulin, prohibitins 1 and 2 and YME1-like-1. Knockdown of CNPY2 in Huh7 and HepG2 human liver cancer cells resulted in significant suppression of cell survival and invasive potential, inhibition of cyclin D1, induction of p21^Waf1/Cip1 and suppression of the apoptosis inhibitor Bcl2. In contrast, transfection of a mouse CNPY2 (mCNPY2-Ds-Red) vector plasmid in Huh7 and HepG2 cancer cells, with subsequent accumulation of CNPY2 in the ER, resulted in significant increase in cancer cells survival. Clinicopathological analysis in 90 HCV-positive HCC patients, revealed significant association of CNPY2 overexpression with poor overall (p = 0.041) survival. Furthermore, CNPY2 increase was associated with vessel invasion (p = 0.038), poor histological differentiation (p = 0.035) and advanced clinical stage (p = 0.016). In conclusion, CNPY2 is a promising molecular target elevated early in hepatocarcinogenesis and prognostic marker for human HCV-associated HCC. CNPY2 is involved in the processes of ER stress, cell cycle progression, proliferation, survival and invasion of liver tumor cells. Full article

A Surface-Enhanced Raman Scattering (SERS) spectrum of 4-cyanopyridine (4CNPy) was recorded on silver plasmonic nanoparticles and analyzed by using Density Functional Theory (DFT) calculations. Two simple molecular models of the metal–4CNPy surface complex with a single silver cation or with a neutral dimer (Ag⁺–4CNPy, Ag₂–4CNPy), linked through the two possible interacting sites of 4CNPy (aromatic nitrogen, N, and nitrile group, CN), were considered. The calculated vibrational wavenumbers and intensities of the adsorbate and the isolated species are compared with the experimental Raman and SERS results. The analysis of the DFT predictions and the experimental data indicates that 4CNPy adsorbs preferentially on neutral/charged active sites of the silver nanoparticles through the nitrogen atom of the aromatic ring with a perpendicular orientation. Full article

Two spin crossover (SCO) coordination polymers assembled by combining Fe^II octahedral ion, 4-cyanopyridine (4-CNpy) and [Au(CN)₂]⁻ liner unit are described. These compounds, Fe(4-CNpy)₂[Au(CN)₂]₂·1/2(4-CNpy) (1a) and {Fe(4-CNpy)₂[Au(CN)₂]₂}-{Fe(H₂O)₂[Au(CN)₂]₂} (1b), present quite different supramolecular networks that show different magnetic behaviors. Compound 1a crystallizes in the centrosymmetric space group Pbcn. The asymmetric unit contains two 4-CNpy, one type of Fe²⁺, and two types of crystallographically distinct [Au(CN)₂]⁻ units which form Hofmann-like two dimensional layer structures with guest spaces. The layers are combined with another layer by strong gold-gold intermetalic interactions. Compound 1b crystallizes in the centrosymmetric space group Pnma. The bent bismonodentate [Au^I(CN)₂] units and Fe^II ions form a complicated interpenetrated three dimensional structure. In addition, 1b exhibits ferromagnetic interaction. Full article