Human Cancer Research Articles

Complete genome sequence of Bulleidia sp. 10714-15 isolated from human colon cancer patients.

Bulleidia sp. is a non-spore-forming, obligatory anaerobic, Gram-positive bacterium isolated from the stool samples of human colon cancer patients. We report the complete genome sequence of Bulleidia sp. 10714-15, comprising a single linear chromosome of 2,218,984 bp with a G + C content of 36.6%.

Epithelial membrane protein 1 in human cancer: a potential diagnostic biomarker and therapeutic target.

Epithelial membrane protein 1 (EMP1) is a member of the small hydrophobic membrane protein subfamily. EMP1 is aberrantly expressed in various tumor tissues and governs multiple cellular behaviors (e.g., proliferation, differentiation, and migration). The resultant regulation of the cancer pathway is responsible for the metastasis of cancer cells and determines the risk of malignant tumor progression. This review provides an updated overview of EMP1 as either an oncogene or a tumor suppressor contingent on the cancer type and summarizes its upstream regulators and downstream target genes. This systematic review summarizes our current understanding of the role of EMP1 in malignant tumor development, including critical functional mechanisms and implications for its potential use as the biomarker and therapeutic target.

New Pd(II)-pincer type complexes as potential antitumor drugs: synthesis, nucleophilic substitution reactions, DNA/HSA interaction, molecular docking study and cytotoxic activity.

Two new complexes of Pd(II), [Pd(L1)Cl]Cl (Pd1) and [Pd(L2)Cl]Cl (Pd2), (where L1 = N2,N6-bis(5-methylthiazol-2-yl)pyridine-2,6-dicarboxamide and L2 = N2,N6-di(benzo[d]thiazol-2-yl)pyridine-2.6-dicarboxamide) were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The nucleophilic substitution reactions of complexes with L-Methionine (L-Met), L-Cysteine (L-Cys) and guanosine-5'-monophosphate (5'-GMP) were studied by stopped-flow method at physiological conditions (pH = 7.2 and 37 °C). Complex Pd1 was more reactive than Pd2 in all studied reactions, while the order of reactivity of the selected ligands was: L-Met > L-Cys > 5'-GMP. The interaction of complexes with calf thymus-DNA (CT-DNA) was studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. Both complexes interacted with DNA through intercalation and minor groove binding, where the latter was preferred. Additionally, the interaction of Pd1 and Pd2 complexes with human serum albumin (HSA) was studied employing fluorescence quenching spectroscopy. The results indicate a moderate binding affinity of complexes, with slightly stronger binding of the Pd1. Fluorescence competition experiments with site-markers (eosin Y and ibuprofen) for HSA were used to locate the binding site of Pd1 to the HSA. Additionally, the interaction with DNA and HSA was studied by molecular docking and the revealed results were in good agreement with the experimentally obtained ones. Pd1 complex exhibited cytotoxicity toward human (HCT116) and mouse cell lines (CT26) of colorectal cancer, mouse (4T1) and human (MDA-MB468) breast cancer lines and non-cancerous mouse mesenchymal stem cells (mMSC). In addition, Pd1 complex demonstrated significant selectivity towards cancer cells over non-cancerous mMSC, indicating a high potential to eliminate malignant cells without affecting normal cells. It induced apoptosis in CT26 cells, effectively arrested the cell cycle in the S phase, and selectively down-regulated cyclin D and cyclin E. Moreover, it can alter the expression of cell cycle regulators by increasing p21 and decreasing p-AKT. These findings confirm its ability to disrupt key tumor cell survival signals and suggest that the Pd1 complex is a potent candidate for effective cancer treatment.

A bibliometric and visualization analysis of entosis research from 2007 to 2024

ObjectiveIn 2007, entosis was proposed as a form of programmed cell death, distinct from apoptosis. This process involves a living cell (internalized cell) actively invading a neighboring live cell of the same type (host cell), forming a cell-in-cell structure. Recently, entosis has been increasingly associated with cancer, leading to significant advancements in research. Despite this progress, a comprehensive and unbiased review of the current state of entosis research is lacking. This study aims to evaluate the developments in the field of entosis over the past decade and highlight emerging research trends.Materials and methodsWe performed a literature search for studies published since the introduction of the entosis concept, using the Web of Science Core Collection database. The bibliometric analysis was conducted using VOSviewer, CiteSpace, Microsoft Excel, and the Bibliometrix R package.ResultsA total of 196 articles from 39 countries and 346 institutions were included. Between 2007 and 2024, research on entosis has seen rapid growth, with most publications originating from China and the United States. The United States also leads in total citations, with Memorial Sloan Kettering Cancer Center emerging as the top research institution. Sun Qiang is the most prolific author in this field, while Overholtzer M has the highest number of citations. Current Molecular Medicine has published the most articles related to entosis. Frequently occurring keywords include “entosis,” “cannibalism,” “autophagy,” and “apoptosis.” In recent years, keywords such as “phagocytosis,” “drug resistance,” and “human cancers” have surged, indicating a growing focus on understanding the role of entosis in tumor progression and exploring its potential as a therapeutic target for cancer treatment.ConclusionsThis study provides the first bibliometric analysis of entosis, detailing its evolution over the last decade. It highlights critical areas of interest, including the development of inhibitors targeting entosis and their potential clinical applications. This research aims to guide future investigations and serve as a valuable resource for scholars exploring entosis in cancer biology.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer have poor outcomes. Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer. Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not yet been reported. AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer. METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly divided into two groups: One group received inetetamab combined with the SOX regimen, and the other group received trastuzumab combined with the SOX regimen. After 4-6 cycles, patients with stable disease received maintenance therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were the objective response rate, disease control rate, and adverse events (AEs). RESULTS Thirty-seven patients completed the trial, with 18 patients in the inetetamab group and 19 patients in the trastuzumab group. In the inetetamab group, the median PFS was 8.5 months, whereas it was 7.3 months in the trastuzumab group (P = 0.046); this difference was significant. The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months (P = 0. 33), and the objective response rate was 50% vs 42% (P = 0.63), respectively; these differences were not significant. Common AEs included leukopenia, thrombocytopenia, nausea, and vomiting. The incidence rates of grade ≥ 3 AEs were 56% in the inetetamab group and 47% in the trastuzumab group (P = 0.63), with no significant difference. CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer, inetetamab and trastuzumab showed comparable efficacy. The inetetamab group showed superior PFS, and both groups had good safety.

MICU2 up-regulation enhances tumor aggressiveness and metabolic reprogramming during colorectal cancer development.

The mitochondrial Ca2+ uniporter (MCU) plays crucial role in intramitochondrial Ca2+ uptake, allowing Ca2+-dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2) to pathophysiological conditions has been poorly investigated. Here, we describe the role of MICU2 in cell proliferation and invasion using in vitro and in vivo models of human colorectal cancer (CRC). Transcriptomic analysis demonstrated an increase in MICU2 expression and the MICU2/MICU1 ratio in advanced CRC and CRC-derived metastases. We report that expression of MICU2 is necessary for mitochondrial Ca2+ uptake and quality of the mitochondrial network. Our data reveal the interplay between MICU2 and MICU1 in the metabolic flexibility between anaerobic glycolysis and OXPHOS. Overall, our study sheds light on the potential role of the MICUs in diseases associated with metabolic reprogramming.

Transcriptomic analysis of cellular senescence induced by ectopic expression of ATF6α in human breast cancer cells.

The transcriptomic profile of cellular senescence is strongly associated with distinct cell types, the specific stressors triggering senescence, and temporal progression through senescence stages. This implies the potential necessity of conducting separate investigations for each cell type and a stressor inducing senescence. To elucidate the molecular mechanism that drives endoplasmic reticulum (ER) stress-induced cellular senescence in MCF-7 breast cancer cells, with a particular emphasis on the ATF6α branch of the unfolded protein response. We conducted transcriptomic analysis on MCF-7 cells by ectopic expression of ATF6α. Transcriptomic sequencing was conducted on MCF-7 cells at 6 and 9 hours post senescence induction through ATF6α ectopic expression. Comprehensive analyses encompassing enriched functional annotation, canonical pathway analysis, gene network analysis, upstream regulator analysis and gene set enrichment analysis were performed on Differentially Expressed Genes (DEGs) at 6 and 9 hours as well as time-related DEGs. Regulators and their targets identified from the upstream regulator analysis were validated through RNA interference, and their impact on cellular senescence was assessed by senescence-associated β-galactosidase staining. ATF6α ectopic expression resulted in the identification of 12 and 79 DEGs at 6 and 9 hours, respectively, employing criteria of a false discovery rate < 0.05 and a lower fold change (FC) cutoff |log2FC| > 1. Various analyses highlighted the involvement of the UPR and/or ER Stress Pathway. Upstream regulator analysis of 9 hour-DEGs identified six regulators and eleven target genes associated with processes related to cytostasis and 'cell viability and cell death of connective tissue cells.' Validation confirmed the significance of MAP2K1/2, GPAT4, and PDGF-BB among the regulators and DDIT3, PPP1R15A, and IL6 among the targets. Transcriptomic analyses and validation reveal the importance of the MAP2K1/2/GPAT4-DDIT3 pathway in driving cellular senescence following ATF6α ectopic expression in MCF-7 cells. This study contributes to our understanding of the initial molecular events underlying ER stress-induced cellular senescence in breast cancer cells, providing a foundation for exploring cell type- and stressor-specific responses in cellular senescence induction.

Developmental-status-aware transcriptional decomposition establishes a cell state panorama of human cancers

BackgroundCancer cells evolve under unique functional adaptations that unlock transcriptional programs embedded in adult stem and progenitor-like cells for progression, metastasis, and therapeutic resistance. However, it remains challenging to quantify the stemness-aware cell state of a tumor based on its gene expression profile.MethodsWe develop a developmental-status-aware transcriptional decomposition strategy using single-cell RNA-sequencing-derived tissue-specific fetal and adult cell signatures as anchors. We apply our method to various biological contexts, including developing human organs, adult human tissues, experimentally induced differentiation cultures, and bulk human tumors, to benchmark its performance and to reveal novel biology of entangled developmental signaling in oncogenic processes.ResultsOur strategy successfully captures complex dynamics in developmental tissue bulks, reveals remarkable cellular heterogeneity in adult tissues, and resolves the ambiguity of cell identities in in vitro transformations. Applying it to large patient cohorts of bulk RNA-seq, we identify clinically relevant cell-of-origin patterns and observe that decomposed fetal cell signals significantly increase in tumors versus normal tissues and metastases versus primary tumors. Across cancer types, the inferred fetal-state strength outperforms published stemness indices in predicting patient survival and confers substantially improved predictive power for therapeutic responses.ConclusionsOur study not only provides a general approach to quantifying developmental-status-aware cell states of bulk samples but also constructs an information-rich, biologically interpretable, cell-state panorama of human cancers, enabling diverse translational applications.

Investigation of antibacterial and anticancer activities of biosynthesized metal-doped and undoped zinc oxide nanoparticles.

Over the past 10 years, nanotechnology has emerged as a very promising technique for a wide range of biomedical applications. Green synthesized metal and metal oxide nanoparticles (NPs) are cheap, easy to produce in large quantities, and safe for the environment. Currently, efforts are being made to dope ZnO in order to improve its optical, electrical, and ferromagnetic qualities as well as its crystallographic quality. Actually, doping is one of the simplest methods for enhancing an NP's physicochemical characteristics because it involves introducing impure ions into the crystal lattice of the particle. In this study, the biosynthesis of zinc oxide NPs (ZnONPs) and metal-doped (Mg2+ and Ag+) ZnONPs was carried out by using aqueous and water-alcoholic extracts of Cynara scolymus L. leaves, Carthamus tinctorius L. flowers, and Rheum ribes L. (RrL) plant, which are rich in phytochemical content. Plant extracts act as a natural reducing, capping, and stabilizing agent in the production. The produced NPs were characterized using a variety of methods, such as ultraviolet-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM). The produced metal-doped and undoped ZnONPs exhibited characteristic absorption peaks between 365 and 383nm due to their surface plasmon resonance bands. SEM analysis revealed that the NPs were oval, nearly spherical, and spherical. In the FTIR spectra, the Zn-O bonding peak ranges from 400 to 700cm-1. The peaks obtained in the range of 407-562cm-1 clearly represent the Zn-O bond. In addition, the FTIR results showed that there were notable amounts of phenol and flavonoid compounds in both the prepared extract and ZnONPs. According to DLS analysis results, the size distribution of produced NPs is between 120 and 786nm. The antibacterial properties of green produced NPs on Gram-positive (Staphylococcus aureus RN4220) and Gram-negative (Escherichia coli DH10B) bacterial strains were investigated by agar well diffusion method. In studies investigating the anticancer activities of biosynthesized NPs, mouse fibroblast cells (L929) were used as healthy cells and human cervical cancer cells (HeLa) were used as cancer cells. Only the produced Ag-ZnONPs showed potent dose-dependent antibacterial activity (at concentrations higher than 100µg/mL) against Gram-positive and Gram-negative bacteria. RrL-ZnONP-600 and RrL-ZnONP-800 NPs produced with water-ethanol extract of RrL plant and calcined at 600 and 800°C were effective at high concentrations in healthy cells and at low concentrations in HeLa cancer cells, showing that they have the potential to be anticancer agents. The study's findings highlight the potential of green synthesis techniques in the production of medicinal nanomaterials for the treatment of cancer and other biological uses.

Pre-Defined Stem-Loop Structure Library for the Discovery of L-RNA Aptamers that Target RNA G-Quadruplexes.

L-RNA aptamers have been developed to target G-quadruplexes (G4s) and regulate G4-mediated gene expression. However, the aptamer selection process is laborious and challenging, and aptamer identification is subjected to high failure rate. By analyzing the previously reported G4-binding L-RNA aptamers, we found that the stem-loop (SL) structure is favored by G4 binding. Herein, we present a robust and effective G4-SLSELEX-Seq platform specifically for G4 targets by introducing a pre-defined stem-loop structure library during SELEX process. Using G4-SLSELEX-Seq, we rapidly identified an L-RNA aptamer, L-Apt1-12 for EBNA1 RNA G4 (rG4) in just three selection rounds. L-Apt1-12 maintained the stem-loop structure initially introduced, and possessed a unique G-triplex motif that is important for the strong binding affinity and specificity to EBNA1 rG4. Notably, L-Apt1-12 effectively downregulated endogenous EBNA1 protein expression in human cancer cells and showed selective toxicity towards EBV-positive cancer cells, highlighting its potential for targeted therapy against EBV-associated cancers. Furthermore, we demonstrate the robustness and generality of G4-SLSELEX-Seq by selecting L-RNA aptamers for another two G4 targets-APP rG4 and HCV-1a rG4, also obtaining high-affinity aptamers in three selection rounds. These findings demonstrated G4-SLSELEX-Seq can be a robust and efficient platform for the selection of L-RNA aptamers targeting rG4.

Pre‐Defined Stem‐Loop Structure Library for the Discovery of L‐RNA Aptamers that Target RNA G‐Quadruplexes

L‐RNA aptamers have been developed to target G‐quadruplexes (G4s) and regulate G4‐mediated gene expression. However, the aptamer selection process is laborious and challenging, and aptamer identification is subjected to high failure rate. By analyzing the previously reported G4‐binding L‐RNA aptamers, we found that the stem‐loop (SL) structure is favored by G4 binding. Herein, we present a robust and effective G4‐SLSELEX‐Seq platform specifically for G4 targets by introducing a pre‐defined stem‐loop structure library during SELEX process. Using G4‐SLSELEX‐Seq, we rapidly identified an L‐RNA aptamer, L‐Apt1‐12 for EBNA1 RNA G4 (rG4) in just three selection rounds. L‐Apt1‐12 maintained the stem‐loop structure initially introduced, and possessed a unique G‐triplex motif that is important for the strong binding affinity and specificity to EBNA1 rG4. Notably, L‐Apt1‐12 effectively downregulated endogenous EBNA1 protein expression in human cancer cells and showed selective toxicity towards EBV‐positive cancer cells, highlighting its potential for targeted therapy against EBV‐associated cancers. Furthermore, we demonstrate the robustness and generality of G4‐SLSELEX‐Seq by selecting L‐RNA aptamers for another two G4 targets‐APP rG4 and HCV‐1a rG4, also obtaining high‐affinity aptamers in three selection rounds. These findings demonstrated G4‐SLSELEX‐Seq can be a robust and efficient platform for the selection of L‐RNA aptamers targeting rG4.

Detection of PIK3CA hotspot mutations in canine mammary tumors using droplet digital PCR: tissue validation and liquid biopsy feasibility

Domestic dogs (Canis lupus familiaris) serve as valuable translational models for human cancer research due to their biological similarities. Canine mammary tumors (CMTs), frequently diagnosed in female dogs, share various characteristics with human breast cancers. This study investigates the PIK3CA (H1047R) mutation in CMTs using droplet digital PCR (ddPCR) and explores the potential of liquid biopsy for non-invasive detection. We analyzed 80 formalin-fixed, paraffin-embedded (FFPE) CMT tissue samples and compared ddPCR results with next-generation sequencing (NGS) data, achieving high concordance. Plasma and serum samples were also assessed for mutation concordance with tissue results. Our findings indicate a higher frequency of the PIK3CA (H1047R) mutations in benign and grade I malignant CMTs compared to more aggressive malignancies. The ddPCR assay demonstrated high sensitivity and specificity, with plasma testing showing 78.6% sensitivity and 87.5% specificity, and serum testing showing 66.7% sensitivity and 90.0% specificity. These results highlight the viability of liquid biopsy as a minimally invasive method for monitoring PIK3CA mutations in canine patients. The study suggests that liquid biopsy techniques hold significant promise for improving the early detection and monitoring of canine cancers, warranting further research to refine these methods and explore their applications in canine cancer diagnostics and treatment.

CancerSCEM 2.0: an updated data resource of single-cell expression map across various human cancers.

The field of single-cell RNA sequencing (scRNA-seq) has advanced rapidly in the past decade, generating significant amounts of valuable data for researchers to study complex tumor profiles. This data is crucial for gaining innovative insights into cancer biology. CancerSCEM (https://ngdc.cncb.ac.cn/cancerscem) is a public resource that integrates, analyzesand visualizes scRNA-seq data related to cancer, and it provides invaluable support to numerous cancer-related studies. With CancerSCEM 2.0, scRNA-seq data have increased from 208 to 1466 datasets, covering tumor, matching-normaland peripheral blood samples across 127 research projects and 74 cancer types. The new version of this resource enhances transcriptome analysis by adding copy number variation evaluation, transcription factor enrichment, pseudotime trajectory construction, and diverse biological feature scoring. It also introduces a new cancer metabolic map at the single-cell level, providing an intuitive understanding of metabolic regulation across different cancer types. CancerSCEM 2.0 has a more interactive analysis platform, including four modules and 14 analytical functions, allowing researchers to perform cancer scRNA-seq data analyses in various dimensions. These enhancements are expected to expand the usability of CancerSCEM 2.0 to a broader range of cancer research and clinical applications, potentially revolutionizing our understanding of cancer mechanisms and treatments.

The Burden and Prevention of Human Papillomavirus (HPV) Infections and Cervical Cancer in India: A Literature Review

The Burden and Prevention of Human Papillomavirus (HPV) Infections and Cervical Cancer in India: A Literature Review

Multilevel Disparities of Sex-Differentiated Human Papilloma Virus-Positive Oropharyngeal Cancers in the United States

Multilevel Disparities of Sex-Differentiated Human Papilloma Virus-Positive Oropharyngeal Cancers in the United States

Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.

The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8+ T cells and to the suppression of the formation of regulatory T cells. Notably, activating and expanding chimaeric antigen receptor (CAR) T cells with SynVACs led to a CAR-transduction efficiency of approximately 90% and to substantial increases in T memory stem cells. The engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, persisted for longer periods and reduced tumour-recurrence risk. Our findings underscore the crucial roles of viscoelasticity in T-cell engineering and highlight the utility of SynVACs in cancer therapy.

A scoping review of human papillomavirus and cervical cancer knowledge, attitudes, practices, and prevention among female sex workers in Africa

Background Global initiatives have emphasized the elimination of cervical cancer (CC) among female sex workers (FSW) in Africa. Yet screening remains low, and few interventions have been outlined to target this group. This scoping review sought to understand the knowledge, attitudes, and practices (KAP) among FSW in Africa regarding human papillomavirus (HPV) and CC prevention, and to identify the most effective intervention strategies. Methods A systematic literature search was performed in PubMed, Scopus, Web of Science, and African Index Medicus for work published between January 2012 through August 2022. Eligible studies included those relating to HPV and CC prevention among FSW in Africa. Studies were categorized as KAP, intervention, or both. A Logic Model was used to guide content analysis of the interventions, and a thematic analysis of all studies was performed. Results The search resulted in 79 articles of which 11 were included in the study. Six African countries were represented including South Africa, Mozambique, Uganda, Kenya, Ethiopia, and Nigeria. Five of the articles described KAP, while the other six described interventions. The intervention studies were categorized into 3 groups: “screen and treat”, self-collection HPV testing, and a “diagonal intervention” which included a multi-faceted approach. Conclusions Limited literature exists regarding KAP and interventions for HPV and CC prevention among FSW in Africa. While FSW in the literature had a moderate level of knowledge regarding HPV and CC prevention, studies identified a lack of detailed and nuanced knowledge. Successful uptake of screening was seen when services were provided at convenient locations, integrated into routine or HIV care, and recommended by healthcare providers. Future interventions should be context-specific, include improved counselling and education, and be integrated with other services.

PhosphazeneTripeptide Conjugates: Design, Synthesis,In VitroCytotoxicity and Genotoxicity, Molecular Interactions in Binding Pockets on Human Breast and Colon Cancer Cell Lines.

The biological activity of both cyclophosphazenes and peptides makes these compounds important for new studies in medicinal chemistry. For this purpose, five different phosphazene-peptide conjugates synthesized from dichlorocyclotriphosphazene and tyrosine-containing tripeptides. The synthesized compounds were evaluated for their in vitro cytotoxic activities against human breast (MCF-7) and colon (Caco-2) cancer cell lines using MTT assay. The derivatives induced cell death through DNA damage, with notable effects in Caco-2 cell lines. Specifically, DTVV, DTVG, and DTVA were cytotoxic at 50 and 100 µM, while DTVP and DTVM were effective at 25, 50, and 100 µM. DTVM outperformed Tamoxifen at 50 µM in the MCF-7 cell line. DNA damage studies of the compounds were performed using the comet assay method.The findings indicated that cell death occurred via a DNA damage mechanism. The molecular intricacies of DTVA, DTVG, DTVM, DTVP and DTVV within the VEGFR2 kinase domainand Cyclophilin_CeCYP16-Like Domainbinding pockets and various interactions, docking scores and potential activities of these derivatives were investigated. The differences in docking scores and interaction profiles highlight the potential efficacy and specificity of these compounds in targeting breast and colon cancer cells. These findings highlight the potential of phosphazene-peptide derivatives as therapeutic agents in cancer treatment.

Potential antitumor effect of polysaccharides extracted from Polygonatum sibiricum on human prostate cancer PC‑3 cells

Potential antitumor effect of polysaccharides extracted from <i>Polygonatum sibiricum</i> on human prostate cancer PC‑3 cells

HCP5 Derived Novel Microprotein Triggers Progression of Gastric Cancer through Regulating Ferroptosis.

The context of long noncoding RNAs (lncRNAs) contains many unannotated open reading frames (ORFs). These ORFs potentially encode novel proteins or peptides with crucial roles in various human cancers, yet the translational potential of these lncRNAs and the functions of the protein products remain largely unexplored, especially in gastric cancer (GC). In this study, a comprehensive analysis is performed and identified a GC associated lncRNA known as HCP5, which contains a non-canonical ORF. Further analysis showed that HCP5-132aa, a microprotein encoded by HCP5 harboring this ORF, is highly expressed in GC cells and tissues, and can promote the proliferation of GC cells by inhibiting ferroptosis. Mechanistically, HCP5-132aa enhances the interaction between YBX1 and ELAVL1, facilitates recognition of YBX1 at the m5C site in the 3'UTR of SLC7A11 and G6PD mRNA, and preserves their stability via ELAVL1. By employing a Cas9/sgRNA delivery system with AAV in vivo, effectively knocked out the HCP5-132aa and inhibition of tumor growth in a patient-derived xenograft model are achieved. These findings demonstrate that the novel protein HCP5-132aa, derived from lncRNA HCP5, mediates the repression of ferroptosis, thereby driving the progression of GC and identifying a new potential therapeutic target for its treatment.