The natural product micheliolide promotes the nuclear translocation of GAPDH via binding to Cys247 and induces glioblastoma cell death in combination with temozolomide.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is significantly upregulated in glioblastoma (GBM) and plays a crucial role in cell apoptosis and drug resistance. Micheliolide (MCL) is a natural product with a variety of antitumour activities, and the fumarate salt form of dimethylamino MCL (DMAMCL; commercial name ACT001) has been tested in clinical trials for recurrent GBM; this compound suppresses the proliferation of GBM cells by rewiring aerobic glycolysis. Herein, we demonstrated that MCL directly targets GAPDH through covalent binding to the cysteine 247 (Cys247) residue.

Discovery of indole analogue Tc3 as a potent pyroptosis inducer and identification of its combination strategy against hepatic carcinoma.

Hepatic carcinoma, one of the most malignant cancers in the world, has limited success with immunotherapy and a poor prognosis in patients. While pyroptosis is considered as a promising immunotherapy strategy for tumors, it still suffers from a lack of effective inducers. We designed, synthesized and screened an indole analogue, , featuring a 2, 4-thiazolidinedione substituted indole scaffold.

Discovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.

Histone lysine-specific demethylase 1 (LSD1) is overexpressed in various solid and hematological tumors, suggesting its potential as a therapeutic target, but there are currently no LSD1 inhibitors available on the market. In this study we employed a computer-guided approach to identify novel LSD1/EGFR dual inhibitors as a potential therapeutic agent for non-small cell lung cancer. Through a multi-stage virtual screening approach, we found L-1 and L-6, two compounds with unique scaffolds that effectively inhibit LSD1 with IC values of 6.

Identification of TAT as a Biomarker Involved in Cell Cycle and DNA Repair in Breast Cancer.

Breast cancer (BC) is the most frequently diagnosed cancer and the primary cause of cancer-related mortality in women. Treatment of triple-negative breast cancer (TNBC) remains particularly challenging due to its resistance to chemotherapy and poor prognosis. Extensive research efforts in BC screening and therapy have improved clinical outcomes for BC patients.

The eEF1A protein in cancer: Clinical significance, oncogenic mechanisms, and targeted therapeutic strategies.

Eukaryotic elongation factor 1A (eEF1A) is among the most abundant proteins in eukaryotic cells. Evolutionarily conserved across species, eEF1A is in charge of translation elongation for protein biosynthesis as well as a plethora of non-translational moonlighting functions for cellular homeostasis. In malignant cells, however, eEF1A becomes a pleiotropic driver of cancer progression via a broad diversity of pathways, which are not limited to hyperactive translational output.

SF3B3-regulated mTOR alternative splicing promotes colorectal cancer progression and metastasis.

Background: Aberrant alternative splicing (AS) is a pervasive event during colorectal cancer (CRC) development. SF3B3 is a splicing factor component of U2 small nuclear ribonucleoproteins which are crucial for early stages of spliceosome assembly. The role of SF3B3 in CRC remains unknown.

Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (mA) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of mA modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive.

Malate, a natural inhibitor of 6PGD, improves the efficacy of chemotherapy in lung cancer.

Objective: Metabolic reprogramming is an important coordinator of tumor development and resistance to therapy, such as the tendency of tumor cells to utilize glycolytic energy rather than oxidative phosphorylation, even under conditions of sufficient oxygen. Therefore, targeting metabolic enzymes is an effective strategy to overcome therapeutic resistance.

Materials And Methods: We explored the differential expression and growth-promoting function of MDH2 by immunohistochemistry and immunoblotting experiments in lung cancer patients and lung cancer cells.

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1.

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action.

Transcriptome analysis identifies genetic risk markers and explores the pathogenesis for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an incurable and disabling bowel disease driven by multiple risk factors that severely limit patients' quality of life. We integrated the RNA-sequencing data of 1238 IBD patients, and investigated the pathogenesis of IBD by combining transcriptional element prediction analysis and immune-related analysis. Here, we first determined that KIAA1109 is inhibited in IBD patients.

Tyrosine metabolic reprogramming coordinated with the tricarboxylic acid cycle to drive glioma immune evasion by regulating PD-L1 expression.

Due to the existence of the blood-brain barrier in glioma, traditional drug therapy has a poor therapeutic outcome. Emerging immunotherapy has been shown to have satisfactory therapeutic effects in solid tumors, and it is clinically instructive to explore the possibility of immunotherapy in glioma. We performed a retrospective analysis of RNA-seq data and clinical information in 1027 glioma patients, utilizing machine learning to explore the relationship between tyrosine metabolizing enzymes and clinical characteristics.

Glucose-6-phosphate dehydrogenase: a therapeutic target for ovarian cancer.

Introduction: Ovarian cancer (OC) is a gynecological tumor disease, which is usually diagnosed at an advanced stage and has a poor prognosis. It has been established that the glucose metabolism rate of cancer cells is significantly higher than that of normal cells, and the pentose phosphate pathway (PPP) is an important branch pathway for glucose metabolism. Glucose-6-phosphate dehydrogenase (G6PD) is the key rate-limiting enzyme in the PPP, which plays an important role in the initiation and development of cancer (such as OC), and has been considered as a promisinganti-cancer target.

A model for identification of potential phase-separated proteins based on protein sequence, structure and cellular distribution.

The cells are like a highly industrialized and urbanized city, filled with numerous biological macromolecules and metabolites, forming a crowded environment. While, the cells have compartmentalized organelles to complete different biological processes efficiently and orderly. However, membraneless organelles are more dynamic and adaptable for transient events including signal transduction and molecular interactions.

PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1.

Protein arginine methyltransferase 5 (PRMT5) is a major type II enzyme responsible for symmetric dimethylation of arginine (SDMA), and plays predominantly roles in human cancers, including in ovarian cancer. However, the exactly roles and underlying mechanisms of PRMT5 contributing to the progression of ovarian cancer mediated by reprogramming cell metabolism remain largely elusive. Here, we report that PRMT5 is highly expressed and correlates with poor survival in ovarian cancer.

Site-directed late-stage diversification of macrocyclic nannocystins facilitating anticancer SAR and mode of action studies.

Nannocystins are a family of 21-membered cyclodepsipeptides with excellent anticancer activity. However, their macrocyclic architecture poses a significant challenge to structure modification. Herein, this issue is addressed by leveraging the strategy of post-macrocyclization diversification.

PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer.

Genome-wide identification and expression analysis of the bHLH gene family in cauliflower ().

Unlabelled: Basic helix-loop-helix (bHLH) transcription factors (TFs) are one of the largest TF families in plant species, and they play important roles in plant growth, development and stress responses. The present study systematically identified members of the cauliflower ( L.) bHLH gene family based on genomic data.

PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis.

Previous studies have shown that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) is involved in the regulation of several biological processes in cancer. In our previous study, we demonstrated a crucial function of PIKE-A in cancer energy metabolism by regulating pentose phosphate pathway (PPP) flux. However, whether PIKE-A regulates energy metabolism through affecting mitochondrial changes are poorly understood.

PRIM2 Promotes Cell Cycle and Tumor Progression in p53-Mutant Lung Cancer.

p53 is a common tumor suppressor, and its mutation drives tumorigenesis. What is more, p53 mutations have also been reported to be indicative of poor prognosis in lung cancer, but the detailed mechanism has not been elucidated. In this study, we found that DNA primase subunit 2 (PRIM2) had a high expression level and associated with poor prognosis in lung cancer.

The Potential Mechanisms of Cinobufotalin Treating Colon Adenocarcinoma by Network Pharmacology.

Network pharmacology, as a novel way using bioinformatics to explore drug targets and interactions in cancer, broadens our understanding of drug action, thereby facilitating drug discovery. Here, we utilized network pharmacology to explore the role and mechanism by which cinobufotalin functions in colon adenocarcinoma (COAD). We found that cinobufotalin represses the growth and proliferation of colon cancer cells, and integrated public databases for targets reported to be associated with COAD, together with those predicted to be targets of cinobufotalin.

Identification of HGD and GSTZ1 as Biomarkers Involved Metabolic Reprogramming in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of renal cell carcinoma, accounting for more than 80% of patients. Most patients are diagnosed at an advanced stage due to being asymptomatic early on. Advanced KIRC has an extremely poor prognosis due to its inherent resistance to radiotherapy and chemotherapy.

A rational foundation for micheliolide-based combination strategy by targeting redox and metabolic circuit in cancer cells.

Accumulating evidence has supported that targeting oxidative stress and metabolic alterations of cancer is an effective strategy to combat cancer. We previously reported that Dimethylaminomicheliolide (DMAMCL) and its active metabolite micheliolide (MCL) can cause oxidative stress and cell death in leukemia and glioblastoma. However, the detailed mechanism underlying MCL or DMAMCL triggered oxidative stress remains elusive.