[Anti-breast cancer effect of a mitochondrion-targeted derivative of ergosterol peroxide in vitro and in vivo].

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 µmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 µmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 µmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 µmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P<0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.

Effects of Isoxazolyl Steroids on Key Genes of Sonic Hedgehog Cascade Expression in Tumor Cells.

Activation of the Hedgehog (Hh) signaling pathway is often associated with the progression of various types of cancer. The purpose of study was to search for inhibitors of the Hh signaling pathway among eight compounds belonging to the group of isoxazolyl steroids. The evaluation of the effectiveness of the compounds was based on the analysis of their cytotoxicity, effect on the cell cycle, on the expression of key Hh-signaling-pathway genes (Ptch1, Smo, and Gli1) and putative target genes MMP-2 and MMP-9. Four compounds with the most pronounced cytotoxic effect were identified: compounds 1, 2 (HeLa cells) and 3, 4 (A549 cells). Compounds 1 and 2 significantly reduced the expression of the Ptch1, Smo, Gli1 genes, but had the opposite effect on MMP-2 gene expression: Compound 1 increased it, and compound 2 decreased it. Compounds 3 and 4 did not have a noticeable inhibitory effect on the expression of the Shh pathway receptors, but significantly inhibited MMP-2 and MMP-9 expression. Thus, it was shown that inhibition of the Shh signaling pathway by isoxazolyl steroids can have the opposite effect on MMPs gene expression, which is what should be taken into account in further studies of these compounds as therapeutic agents.

Forebrain Eml1 depletion reveals early centrosomal dysfunction causing subcortical heterotopia.

Subcortical heterotopia is a cortical malformation associated with epilepsy, intellectual disability, and an excessive number of cortical neurons in the white matter. Echinoderm microtubule-associated protein like 1 (EML1) mutations lead to subcortical heterotopia, associated with abnormal radial glia positioning in the cortical wall, prior to malformation onset. This perturbed distribution of proliferative cells is likely to be a critical event for heterotopia formation; however, the underlying mechanisms remain unexplained. This study aimed to decipher the early cellular alterations leading to abnormal radial glia. In a forebrain conditional Eml1 mutant model and human patient cells, primary cilia and centrosomes are altered. Microtubule dynamics and cell cycle kinetics are also abnormal in mouse mutant radial glia. By rescuing microtubule formation in Eml1 mutant embryonic brains, abnormal radial glia delamination and heterotopia volume were significantly reduced. Thus, our new model of subcortical heterotopia reveals the causal link between Eml1's function in microtubule regulation and cell position, both critical for correct cortical development.

A review on antitumor effect of pachymic acid.

Poria cocos, also known as Jade Ling and Songbai taro, is a dry fungus core for Wolfiporia cocos, which is parasitic on the roots of pine trees. The ancients called it "medicine of four seasons" because of its extensive effect and ability to be combined with many medicines. Pachymic acid (PA) is one of the main biological compounds of Poria cocos. Research has shown that PA has various pharmacological properties, including anti-inflammatory and antioxidant. PA has recently attracted much attention due to its anticancer properties. Researchers have found that PA showed anticancer activity by regulating apoptosis and the cell cycle in vitro and in vivo. Using PA with anticancer drugs, radiotherapy, and biomaterials could also improve the sensitivity of cancer cells and delay the progression of cancer. The purpose of this review was to summarize the anticancer mechanism of PA by referencing the published documents. A review of the collected data indicated that PA had the potential to be developed into an effective anticancer agent.

miR-200c targeting GLI3 inhibits cell proliferation and promotes apoptosis in non-small cell lung cancer cells.

Lung cancer is a common malignant tumor with low cure rate. It has an easy recurrence and metastasis. This study explored whether miR-200c could regulate the biological behavior of non-small cell lung cancer cells through targeting GLI3. Luciferase reporter gene analysis was used to verify the interaction between miR-200c-3p and GLI3. miR-200c-3p and GLI3 were transiently overexpressed into A549 cells. The cell viability rate was detected by cell counting kit-8, cell invasion ability was detected with Transwell, cell apoptosis and cell cycle was determined by flow cytometry, and the expression of GLI3 was detected using quantitative polymerase chain reaction and Western blot, to verify the effect of the interaction between miR-200c-3p and GLI3 on the cell activities. miR-200c-3p overexpression could inhibit cell viability and invasion, promote apoptosis, induce G0/G1 arrest, and inhibit cell division. GLI3 overexpression could reverse the miR-200c-3p inhibition on cell cycle, reduce the number of cells in the G0/G1 phase and increase the number of cells in the S phase. miR-200c-3p overexpression in A549 cells could inhibit cell viability and invasion, and promote apoptosis. miR-200c-3p could target GLI3 to regulate cell cycle and inhibit cell proliferation.

Anti-tumor potential of high salt in breast Cancer cell lines.

BACKGROUND: Recent 23Na-MRI reports show higher salt deposition in malignant breast tissue than in surrounding normal tissue. The effect of high salt on cancer progression remains controversial. Here, we investigated the direct effect of high salt on breast cancer progression in vitro. METHODS: Here, the impact of high salt on apoptosis, proliferation, cell cycle, adhesion, and migration of MDA-MB-231 and MCF-7 cells was studied using MTT, scratch, and clonogenic assays, as well as RT-PCR and flow cytometry. Gene expression was analyzed using Real-Time PCR and western blotting. The effect of high salt on global transcriptomics changes in MDA MB-231 cells was studied using RNA-sequencing analysis. RESULTS: Flow cytometry with Annexin V and CFSE revealed that high salt-induced dose-dependent apoptosis and inhibited proliferation. High salt-induced cell cycle arrest at the G1/S phase of the cell cycle. p-MDM2 is known to suppress p53, which plays a crucial role in regulating apoptosis and cell cycle arrest under cellular stress conditions. High salt treatment led to decreased p-MDM2 and increased p53 expression, suggesting that high salt induces apoptosis through p53 stabilization. decreased p-MDM2 and increased p53 expression. High salt also reduced migration and adhesion of cells in a dose-dependent manner suggesting its inhibitory effect on metastatic properties as evident from wound healing assay. RNA sequencing analysis revealed overexpression of tumor suppressor genes and genes associated with anti-tumor activity (PCDHGA11, EIF3CL, RAVER1, TNFSF15, RANBP3L) and under-expression of genes involved in cancer-promoting activity (MT1X, CLDN14, CSF-2). CONCLUSION: Our results unequivocally demonstrate the anti-tumor efficacy of high salt against breast cancer cells, suggesting its potential as a therapeutic strategy in cancer treatment.

Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that encodes numerous cellular homologs, including cyclin D, G protein-coupled protein, interleukin-6, and macrophage inflammatory proteins 1 and 2. KSHV vCyclin encoded by ORF72, is the homolog of cellular cyclinD2. KSHV vCyclin can regulate virus replication and cell proliferation by constitutively activating cellular cyclin-dependent kinase 6 (CDK6). However, the regulatory mechanism of KSHV vCyclin has not been fully elucidated. In the present study, we identified a host protein named protein arginine methyltransferase 5 (PRMT5) that interacts with KSHV vCyclin. We further demonstrated that PRMT5 is upregulated by latency-associated nuclear antigen (LANA) through transcriptional activation. Remarkably, knockdown or pharmaceutical inhibition (using EPZ015666) of PRMT5 inhibited the cell cycle progression and cell proliferation of KSHV latently infected tumor cells. Mechanistically, PRMT5 methylates vCyclin symmetrically at arginine 128 and stabilizes vCyclin in a methyltransferase activity-dependent manner. We also show that the methylation of vCyclin by PRMT5 positively regulates the phosphorylate retinoblastoma protein (pRB) pathway. Taken together, our findings reveal an important regulatory effect of PRMT5 on vCyclin that facilitates cell cycle progression and proliferation, which provides a potential therapeutic target for KSHV-associated malignancies.

Inhibitory Effects of Royal Jelly and Its Functional Components on the Proliferation of MKN-28 Gastric Cancer Cells.

Royal jelly (RJ) is a natural food product with nutritional value and anticancer activity. However, their effects on gastric cancer are unclear. Here, we show that treatment with 5-320 µg/mL of RJ, ethanol extract (RJEE), and protein hydrolyzate (RJPH) decreased the viability of MKN-28 gastric cancer cells, with a half-maximal inhibitory concentration of 123.22 µg/mL for RJEE. RJ, RJEE, and RJPH increase the lactate dehydrogenase release rate and change the morphology of the cells, resulting in cell shrinkage, nucleoplasm condensation, and the formation of apoptotic bodies. RJ and its functional components stagnated the cell cycle in the G0/G1 phase, accompanied by the accumulation of reactive oxygen species, decreased mitochondrial membrane potential, and increased expression levels of p53 and p21 proteins, caspase-3 activation, and apoptosis. Therefore, RJ, RJEE, and RJPH have potential inhibitory effects on the proliferation of gastric cancer cells.

PP1 phosphatase controls both daughter cell formation and amylopectin levels in Toxoplasma gondii.

Virulence of apicomplexan parasites is based on their ability to divide rapidly to produce significant biomass. The regulation of their cell cycle is therefore key to their pathogenesis. Phosphorylation is a crucial posttranslational modification that regulates many aspects of the eukaryotic cell cycle. The phosphatase PP1 is known to play a major role in the phosphorylation balance in eukaryotes. We explored the role of TgPP1 during the cell cycle of the tachyzoite form of the apicomplexan parasite Toxoplasma gondii. Using a conditional mutant strain, we show that TgPP1 regulates many aspects of the cell cycle including the proper assembly of the daughter cells' inner membrane complex (IMC), the segregation of organelles, and nuclear division. Unexpectedly, depletion of TgPP1 also results in the accumulation of amylopectin, a storage polysaccharide that is usually found in the latent bradyzoite form of the parasite. Using transcriptomics and phospho-proteomics, we show that TgPP1 mainly acts through posttranslational mechanisms by dephosphorylating target proteins including IMC proteins. TgPP1 also dephosphorylates a protein bearing a starch-binding domain. Mutagenesis analysis reveals that the targeted phospho-sites are linked to the ability of the parasite to regulate amylopectin steady-state levels. Therefore, we show that TgPP1 has pleiotropic roles during the tachyzoite cell cycle regulation, but also regulates amylopectin accumulation.

A perturbation approach for refining Boolean models of cell cycle regulation.

Considerable effort is required to build mathematical models of large protein regulatory networks. Utilizing computational algorithms that guide model development can significantly streamline the process and enhance the reliability of the resulting models. In this article, we present a perturbation approach for developing data-centric Boolean models of cell cycle regulation. To evaluate networks, we assign a score based on their steady states and the dynamical trajectories corresponding to the initial conditions. Then, perturbation analysis is used to find new networks with lower scores, in which dynamical trajectories traverse through the correct cell cycle path with high frequency. We apply this method to refine Boolean models of cell cycle regulation in budding yeast and mammalian cells.

m6A modification enhances the stability of CDC25A promotes tumorigenicity of esophagogastric junction adenocarcinoma via cell cycle.

N6-Methyladenosine (m6A) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated m6A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. By profiling transcriptome-wide targets of IGF2BP3 and the m6A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified targets, including targets of the cell cycle pathway, such as CDC25A, CDK4, and E2F1, are critical for AEG progression. Mechanistically, the increased m6A modification of CDC25A accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the m6A/IGF2BP3/CDC25A axis in AEG cells.

The role of HGH1 in breast cancer prognosis: a study on immune response and cell cycle.

BACKGROUND: Breast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA. METHODS: The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1's role in BRCA. RESULTS: IHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells' proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration. CONCLUSION: Biomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

Polyvinyl Alcohol Capped Silver Nanostructures for Fortified Apoptotic Potential Against Human Laryngeal Carcinoma Cells Hep-2 Using Extremely-Low Frequency Electromagnetic Field.

Purpose: : Polyvinyl alcohol-capped silver nanostructures (cAgNSs) were investigated in order to enhance the cytotoxicity, pro-apoptotic, and oxidant patterns of in human laryngeal carcinoma Hep-2 cells by employing a 50 mT electromagnetic field (LEMF) for 30 min. Methods: Wet chemical reduction was used to synthesize the cAgNSs, and after they had been capped with polyvinyl alcohol, they were specifically examined for particle size analysis and structural morphology. To visualize how the silver may attach to the protein targets, a molecular docking study was conducted. Estimation of cytotoxicity, cell cycle progression supported by mRNA expression of three apoptotic-promoting genes and one apoptotic-resisting. Results: Particle size analysis results were a mean particle size of 157.3±0.5 nm, zeta potential value of -29.6 mV±1.5 mV, and polydispersity index of 0.31±0.05. Significantly reduction of IC50 against Hep-2 cells by around 6-fold was concluded. Also, we obtained suppression of the proliferation of Hep-2 cells, especially in the G0/G1 and S phases. Significant enhanced mRNA expression revealed enhanced induced CASP3, p53, and Beclin-1 mediated pro-apoptosis and induced NF-κB mediated autophagy in Hep-2 cells. Augmented levels of GR, ROS and MDA as oxidative stress biomarkers were also obtained. HE staining of Hep-2 cells exposed to cAgNSs and LEMF confirmed the enhanced apoptotic potential comparatively. Conclusion: By conclusion, the developed nano-sized structures with the aid of extremely-low frequency electromagnetic field were successful to fortify the anti-cancer profile of cAgNSs in Hep-2 cells.

p65 signaling dynamics drive the developmental progression of hematopoietic stem and progenitor cells through cell cycle regulation.

Most gene functions have been discovered through phenotypic observations under loss of function experiments that lack temporal control. However, cell signaling relies on limited transcriptional effectors, having to be re-used temporally and spatially within the organism. Despite that, the dynamic nature of signaling pathways have been overlooked due to the difficulty on their assessment, resulting in important bottlenecks. Here, we have utilized the rapid and synchronized developmental transitions occurring within the zebrafish embryo, in conjunction with custom NF-kB reporter embryos driving destabilized fluorophores that report signaling dynamics in real time. We reveal that NF-kB signaling works as a clock that controls the developmental progression of hematopoietic stem and progenitor cells (HSPCs) by two p65 activity waves that inhibit cell cycle. Temporal disruption of each wave results in contrasting phenotypic outcomes: loss of HSPCs due to impaired specification versus proliferative expansion and failure to delaminate from their niche. We also show functional conservation during human hematopoietic development using iPSC models. Our work identifies p65 as a previously unrecognized contributor to cell cycle regulation, revealing why and when pro-inflammatory signaling is required during HSPC development. It highlights the importance of considering and leveraging cell signaling as a temporally dynamic entity.

An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc.

A programmed developmental switch to G / S endocycles results in tissue growth through an increase in cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute to cancer. Much remains unknown, however, about how these iECs affect tissue growth. Using the D. melanogaster wing disc as model, we find that populations of iECs initially increase in size but then subsequently undergo a heterogenous arrest that causes severe tissue undergrowth. iECs acquired DNA damage and activated a Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant and not eliminated from the epithelium. Instead, iECs entered a JNK-dependent and reversible senescent-like arrest. Senescent iECs promoted division of diploid neighbors, but this compensatory proliferation did not rescue tissue growth. Our study has uncovered unique attributes of iECs and their effects on tissue growth that have important implications for understanding their roles in wound healing and cancer.

Biodegradable magnesium based metal materials inhibit the growth of cervical cancer cells.

Traditional chemotherapy drugs for cervical cancer often cause significant toxic side effects and drug resistance problems, highlighting the urgent need for more innovative and effective treatment strategies. Magnesium alloy is known to be degradable and biocompatible. The release of degradation products Mg2+, OH-, and H2 from magnesium alloy can alter the tumor microenvironment, providing potential anti-tumor properties. We explored the innovative use of magnesium alloy biomaterials in the treatment of cervical cancer, investigating how various concentrations of Mg2+ on the proliferation and cell death of cervical cancer cells. The results revealed that varying concentrations of Mg2+ significantly inhibited cervical cancer by arresting the cell cycle in the G0/G1 phase and inducing apoptosis in SiHa cells, effectively reducing tumor cell proliferation. In vivo experiments demonstrated that 20 mM Mg2+ group had the smallest tumor volume, exhibiting a potent inhibitory effect on the biological characteristics of cervical cancer. This enhances the therapeutic potential of this biomaterial as a local anti-tumor therapy and lays a theoretical foundation for the potential application of magnesium in the treatment of cervical cancer.

SMU1 Knockdown Suppresses Gastric Carcinoma Growth, Migration, and Invasion and Modulates the Cell Cycle.

INTRODUCTION: The role of SMU1 in DNA replication and RNA splicing is well-established, yet its specific function and dysregulated mechanisms in gastric cancer (GC) remain inadequately elucidated. This study seeks to investigate the potential oncogenic and progression-promoting effects of SMU1 in GC, with the ultimate goal of informing novel approaches for treatment and diagnosis. METHODS: The study investigated the expression levels of SMU1 in GC and adjacent normal tissues by analyzing data from the TCGA (27 tissue pairs) and GEO (47 tissue pairs) databases. Immunohistochemistry was used to examine 277 tumor tissue and adjacent non-tumor tissue spots from GC tissue chips, along with relevant follow-up information. The study further assessed the proliferation, invasion, and migration capabilities of cells by manipulating SMU1 expression levels and conducting various assays, including CCK-8, EdU incorporation, colony formation, transwells, flow cytometry, and subcutaneous tumorigenesis assays. RESULTS: Our study revealed a significant upregulation of SMU1 mRNA and protein levels in GC tissues compared to adjacent tissues. Univariate and multivariate Cox analysis demonstrated that elevated levels of SMU1 were independent prognostic factors for GC prognosis (P = 0.036). Additionally, median survival analysis indicated a significant association between high SMU1 expression and poor prognosis in GC patients (P = 0.0002). In experiments conducted both in vivo and in vitro, it was determined that elevated levels of SMU1 can enhance the proliferation, invasion, and migration of GC cells, whereas suppression of SMU1 can impede the progression of GC by modulating the G1/S checkpoint of the cell cycle. CONCLUSIONS: Our research introduces the novel idea that SMU1 could serve as a prognostic marker for GC progression, influencing cell proliferation through cell cycle activation. These results offer valuable insights into the understanding, diagnosis, and management of gastric carcinoma.

Anticancer Activity and Mechanism of Action of Couroupita guianensis Bark Decoction in Gastric Adenocarcinoma Cancer Cell Line.

Couroupita guianensis, a medicinal plant autochthonal to South America and South India, is widely used in the ethnomedicine of the indigenous peoples of these regions thanks to its alleged antimicrobial, anti-inflammatory, antioxidant and wound-healing properties. The majority of studies have mainly analyzed organic extracts of the Indian plant's flowers and leaves, with limited research on its bark decoction, traditionally used in Amazonian shamanic medicine. In this study, we investigated the anticancer effects of the bark decoction and its main fractions obtained through chromatographic separation, as well as the underlying molecular mechanisms in AGS gastric cancer cells. Viability, cell proliferation, cell cycle, apoptosis and protein expression related to these processes were evaluated. Both the bark decoction and fraction III significantly inhibited cell viability, and the cytotoxic effect was linked to cell cycle blockade and the induction of apoptosis also through an engulfment of the autophagic flux. Increased expression or activation of the key proteins (p53, p21, cdk2, Bak, caspases, pAMPK, pAkt, beclin, p62 and LC3BII) involved in these processes was observed. The results obtained confirmed an important anticancer effect of C. guianensis bark decoction, providing scientific validation for its use in traditional medicine and highlighting its potential as a therapeutic agent against gastric cancer.

Apoptosis-Cell Cycle-Autophagy Molecular Mechanisms Network in Heterogeneous Aggressive Phenotype Prostate Hyperplasia Primary Cell Cultures Have a Prognostic Role.

Our study highlights the apoptosis, cell cycle, DNA ploidy, and autophagy molecular mechanisms network to identify prostate pathogenesis and its prognostic role. Caspase 3/7 expressions, cell cycle, adhesion glycoproteins, autophagy, nuclear shrinkage, and oxidative stress by flow-cytometry analysis are used to study the BPH microenvironment's heterogeneity. A high late apoptosis expression by caspases 3/7 activity represents an unfavorable prognostic biomarker, a dependent predictor factor for cell adhesion, growth inhibition by arrest in the G2/M phase, and oxidative stress processes network. The heterogeneous aggressive phenotype prostate adenoma primary cell cultures present a high S-phase category (>12%), with an increased risk of death or recurrence due to aneuploid status presence, representing an unfavorable prognostic biomarker, a dependent predictor factor for caspase 3/7 activity (late apoptosis and necrosis), and cell growth inhibition (G2/M arrest)-linked mechanisms. Increased integrin levels in heterogenous BPH cultures suggest epithelial-mesenchymal transition (EMT) that maintains an aggressive phenotype by escaping cell apoptosis, leading to the cell proliferation necessary in prostate cancer (PCa) development. As predictor biomarkers, the biological mechanisms network involved in apoptosis, the cell cycle, and autophagy help to establish patient prognostic survival or target cancer therapy development.

Mitochondrial NME6 Influences Basic Cellular Processes in Tumor Cells In Vitro.

NME6 belongs to the family of nucleoside diphosphate kinase enzymes, whose major role is to transfer the terminal phosphate from NTPs, mostly ATP, to other (d)NDPs via a high-energy intermediate. Beside this basic enzymatic activity, the family, comprising 10 genes/proteins in humans, executes a number of diverse biochemical/biological functions in the cell. A few previous studies have reported that NME6 resides in the mitochondria and influences oxidative phosphorylation while interacting with RCC1L, a GTPase involved in mitochondrial ribosome assembly and translation. Considering the multifunctional role of NME family members, the goal of the present study was to assess the influence of the overexpression or silencing of NME6 on fundamental cellular events of MDA-MB-231T metastatic breast cancer cells. Using flow cytometry, Western blotting, and a wound-healing assay, we demonstrated that the overexpression of NME6 reduces cell migration and alters the expression of EMT (epithelial-mesenchymal transition) markers. In addition, NME6 overexpression influences cell cycle distribution exclusively upon DNA damage and impacts the MAPK/ERK signaling pathway, while it has no effect on apoptosis. To conclude, our results demonstrate that NME6 is involved in different cellular processes, providing a solid basis for future, more precise investigations of its role.