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Earlier, we have identified PTOV1 as a novel interactome of PIN1 in PC-3 cells. This study aims to explore the functional similarity and the common role of both genes in breast cancer cell proliferation. CTG, crystal violet assay, clonogenic assay, wound healing assay, cell cycle analysis, Hoechst staining and ROS measurement were performed to assess cell viability, colony forming potential, cell cycle arrest, nuclear condensation and ROS production after knocking down of PTOV1 and PIN1 by siRNAs in MDA-MB-231 and MCF-7 cells. CO-IP, qPCR and western blot were performedto study interaction, transcriptional and translational regulation of both genes. Knockdown of PTOV1 and PIN1 inhibited the cell proliferation, colony formation, migration, cell cycle, and induced nuclear condensation as well as ROS production. Interaction of PTOV1 and PIN1 was validated by Co-IP in MDA-MB-231 cells. Genes involved in cell proliferation, migration, cell cycle, and apoptosis were regulated by PIN1 and PTOV1. PTOV1 knockdown inhibited Bcl-2, Bcl-xL and inducedBAX, LC3 and Beclin-1expression. Overexpression of PIN1 increased the expression of PTOV1. Knockdown of both genes inhibited the expression of cyclin D1, c-Myc, and β-catenin. PTOV1 and PIN1 interact and exert oncogenic role in MDA-MB-231 cells by sharing the similar expression profile at transcriptional and translational level which can be a promising hub for therapeutic target.

Plants have long been considered as a basis of medicines for different indigenous cultures around the globe. They continue as a prominent source of important phytoconstituents which exhibit significant biological activities. In this study, we performed the phytochemical screening, estimation of total phenolic and flavonoids, antioxidants, and antimicrobial activities of the stem bark of Beilschmiedia roxburghiana Nees using different solvents. The total phenolic and total flavonoid contents ranged from 106.73 ± 1.62 mg GAE/g and 99.32 ± 0.66 mg QE/g (methanol extract) to 65.59 ± 1.79 mg GAE/g and 29.98 ± 0.90 mg QE/g (n-hexane extract), respectively. The maximum 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity with a half-maximal inhibitory concentration (IC50) of 39.86 ± 3.69 μg/mL was observed for methanol extract followed by aqueous (IC50 = 43.55 ± 6.16 μg/mL), ethyl acetate (IC50 = 44.30 ± 5.88 μg/mL), dichloromethane (IC50 = 71.50 ± 4.70 μg/mL), and the lowest activity was observed for n-hexane extract. The disc diffusion method revealed that the ethyl acetate extract exhibited relatively higher activity against Salmonella typhi (ZOI = 13 mm), and moderate activities against Shigella sonnei, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus aureus (ZOI = 12 mm). The methanol and aqueous extracts showed nearly parallel and the n-hexane and dichloromethane extracts exhibited mild antibacterial activities. The results indicated that the polarity index of the extracting solvents amplified the biological activities of the extract. The study is helpful to support the validity of the traditional application of the plant as natural medicine.

Breast cancer is one of the most common cancers with a high mortality rate, underscoring the need to identify new therapeutic targets. Here we report that non-POU domain-containing octamer-binding (NONO) protein is overexpressed in breast cancer and validated the interaction of the WW domain of PIN1 with c-terminal threonine-proline (thr-pro) motifs of NONO. The interaction of NONO with PIN1 increases the stability of NONO by inhibiting its proteasomal degradation, and this identifies PIN1 as a positive regulator of NONO in promoting breast tumor development. Functionally, silencing of NONO inhibits the growth, survival, migration, invasion, epithelial to mesenchymal transition (EMT), and stemness of breast cancer cells in vitro. A human metastatic breast cancer cell xenograft was established in transparent zebrafish (Danio rerio) embryos to study the metastatic inability of NONO-silenced breast cancer cells in vivo. Mechanistically, NONO depletion promotes the expression of the PDL1 cell-surface protein in breast cancer cells. The identification of novel interactions of NONO with c-Jun and β-catenin proteins and activation of the Akt/MAPK/β-catenin signaling suggests that NONO is a novel regulator of Akt/MAPK/β-catenin signaling pathways. Taken together, our results indicated an essential role of NONO in the tumorigenicity of breast cancer and could be a potential target for anti-cancerous drugs. Video Abstract.

While organ‐confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumours with concomitant inhibition of two tumour suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having < 50% 5‐year secondary‐therapy‐free patient survival. Functionally, overexpression of PME‐1, a methylesterase for the catalytic PP2A‐C subunit, inhibits anoikis in PTEN‐deficient PCa cells. In vivo, PME‐1 inhibition increased apoptosis in in ovo PCa tumour xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME‐1‐deficient PC3 cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype known to correlate with increased apoptosis sensitivity. In summary, our results demonstrate that PME‐1 supports anoikis resistance in PTEN‐deficient PCa cells. Clinically, these results identify PME‐1 as a candidate biomarker for a subset of particularly aggressive PTEN‐deficient PCa. A subset of prostate cancer (PCa) tumours present simultaneous inactivation of two tumour suppressor phosphatases; phosphatase and tensin homolog (PTEN) and protein phosphatase 2A (PP2A). PP2A is inhibited via overexpression of PME‐1. Such cancers are particularly aggressive and often relapse from standard therapy, indicating PME‐1 as a potential clinically applicable biomarker for PCa. Mechanistically, PME‐1 expression protects cancer cells from anoikis, promoting their survival outside the primary tumour.

Isaria tenuipes is one of the potent species in the members of the genus Isaria, which is well reported to possess multiple bioactive substances of therapeutic importance. Therefore, an in vitro experimental study was carried to evaluate the bioactivities of the crude methanolic extract from the mycelium of this fungus. The fungus was authenticated through morphological characters and the species discrepancy was resolved using the nuclear rDNA ITS sequence. The methanolic extract was fingerprinted by FTIR. The antioxidant components in terms of total phenols and flavonoids were determined as gallic acid and quercetin equivalents respectively. Antioxidant activities of the methanolic extract was assessed using 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2, 2 -azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS ), Fe chelating activity, and hydroxyl radical scavenging assays. Cytotoxicity of the extract was determined by [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] (MTT) assay on three cancer cell lines: HeLa, HepG2, and PC3. Apoptosis was further studied by propidium iodide (PI) and Annexin-V/PI staining flow cytometric analysis. Anti-proliferation capacity was studied by colony-forming assay. In the present study total phenol content of the dried methanol extract was 148.09 ± 3.51μg gallic acid equivalent/mg and flavonoid was 9.02±0.95 μg quercetin/mg. The antioxidant activities of methanol-water extract (8:2 v/v) from cultured mycelia of I. tenuipes investigated and evaluated with 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay revealed IC value of 5.04mg/ml with an inhibition rate of 74.77% at 10mg/ml and with an iron-chelating assay the chelating ability was recorded to be 86.76% where the IC value was 4.43 mg/ml. In comparison among the antioxidant assays, 2,2 -azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS ) and hydroxyl assay exhibited radical scavenging rate of 44.42% and 49.82% respectively at a concentration of 10 mg/ml. The IC value of the extract in MTT assay was 43.45μg/ml with HeLa cells, 119.33μg/ml with PC3 cells, and 125.55μg/ml with HepG2 cells. In this study, it can be concluded that the crude methanolic extract exhibited potent antioxidant and antiproliferative activities suggesting natural antioxidative and antiproliferative agents.

RNAs play several prominent roles in the cellular environment ranging from structural, messengers, translators, and effector molecules. RNA molecules while performing these roles are associated with several chemical modifications occurring post-transcriptionally, responsible for these supporting vital functions. The recent documentation of surface RNA modification with sialic acid residues has sparked advancement to the framework of RNA modifications. Glycan modification of surface RNA which was previously known to modify only proteins and lipids has opened new vistas to explore how these surface RNA modifications affect the cellular responses and phenotype. This paradigm shift in RNA biology with a vision of \"glycans being all over the cells\" has posed the field with a repertoire of questions and has given headway to the RNA world hypothesis. The review provides a comprehensive overview of glycoRNA discovery with a conceptual understanding of its previous underlying discoveries and their biological consequences with possible insights into the dynamic influence of this modification on their molecular versatility deciding cancer-immunology fate with potential implications of these glycosylation in cellular interaction, signaling, immune regulation, cancer evasion and proliferation.

The fabrication of metal nanoparticles through green synthetic pathways using plant extracts has increased attention due to low cost, benevolent methods, fewer hazardous byproducts, and applications. Silver nanoparticles (AgNPs) were synthesized by reacting to aqueous root extracts of Rubus ellipticus Sm. (RERE) with AgNO3 solution (1 mM) at an ambient condition. The visual change of color from light yellow to reddish brown and the absorption peak at 416-420 nm in the UV-visible spectra indicated the formation of AgNPs in the solution. The shifting of the positions in the FTIR spectra indicated the potential role of the functional groups as capping and stabilizing agents. The powder XRD diffractogram exposed the crystalline nature of the nanoparticles. The surface morphology and the elemental composition of the AgNPs were established by the FESEM and EDX analysis. The TEM images revealed the spherical and monodispersed nanoparticles of size ranging from 13.85 to 34.30 nm with an average of 25.20±7.01 nm (n=10). The biogenic AgNPs showed a better 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with lower IC50 (13.83±0.33 μg/mL) as compared to that of the RERE with IC50 (15.86±4.14 μg/mL). The synthesized AgNPs showed higher zones of inhibition (ZOI) on the agar well diffusion method against Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), and Klebsiella pneumoniae (ATCC 700603). The result of this study highlights the potential benefits of R. ellipticus root extract-based AgNPs for biomedical practices.

Microbes use diverse defence strategies that allow them to withstand exposure to a variety of genome invaders such as bacteriophages and plasmids. One such defence strategy is the use of RNA guided endonuclease called CRISPR-associated (Cas) 9 protein. The Cas9 protein, derived from type II CRISPR/Cas system, has been adapted as a versatile tool for genome targeting and engineering due to its simplicity and high efficiency over the earlier tools such as ZFNs and TALENs. With recent advancements, CRISPR/Cas9 technology has emerged as a revolutionary tool for modulating the genome in living cells and inspires innovative translational applications in different fields. In this paper we review the developments and its potential uses in the CRISPR/Cas9 technology as well as recent advancements in genome engineering using CRISPR/Cas9.

Breast cancer is most common cancer among women worldwide and among different types of breast cancer treatment of triple-negative breast cancer is major challenge, thus identification of specific drivers is required for targeted therapies of this malignancy. The aim of the present study is to elucidate the effects of silencing of CSNK2β gene by small interfering RNA (siRNA) on proliferation, cell cycle and apoptosis in breast carcinoma MDA MB-231 cells. Silencing of CSNK2β in MDA-MB-231(a triple negative cell line) cells resulted in decreased cell viability and colony formation. Cell cycle analysis showed that silencing of CSNK2β arrested MDA MB-231 cells in G2/M phase. We demonstrated that silencing of CSNK2β promoted nuclear condensation and augmented intracellular ROS production. Furthermore, Silencing of CSNK2β in MDA-MB 231 cells modulated the apoptotic machinery- BAX, Bcl-xL and caspase 3; autophagy machinary-Beclin-1 and LC3-1; and inhibited the vital markers (p-ERK, c-Myc, NF-κB, E2F1, PCNA, p38-α) associated with cell proliferation and DNA replication pathways. In addition, Knocking down of CSNK2 β also affected the migration potential of MDA-MB231 as observed in the wound healing and transwell migration assays. Together, our study suggests that CSNK2β silencing may offer future therapeutic target in triple negative breast cancer.

While organ-confined PCa is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumors with concomitantly compromised function of two tumor suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having less than 50% 5-year secondary-therapy free patient survival. Functionally, overexpression of PME-1, a PP2A inhibitor protein, inhibits anoikis in PTEN-deficient PCa cells. In vivo, PME-1 inhibition increased apoptosis in in ovo PCa tumor xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME-1 deficient PCa cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype corresponding to increased apoptosis sensitivity. In summary, we discover that PME-1 overexpression supports anoikis resistance in PTEN-deficient PCa cells. Clinically, the results identify PME-1 as a candidate biomarker for a subset of particularly aggressive PTEN-deficient PCa. Competing Interest Statement The authors have declared no competing interest.