Modern biology of extrachromosomal DNA: A decade-long voyage of discovery.

Genomic instability is a hallmark of cancer and is a major driving force of tumorigenesis. A key manifestation of genomic instability is the formation of extrachromosomal DNAs (ecDNAs) - acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct from chromosomes. Ontological studies have revealed that ecDNA serves as a carrier of oncogenes, immunoregulatory genes, and enhancers, capable of driving elevated transcription of its cargo genes and cancer heterogeneity, leading to rapid tumor evolution and therapy resistance.

Intratumor Mycoplasma promotes the initiation and progression of hepatocellular carcinoma.

The carcinogenesis and progression of hepatocellular carcinoma (HCC) are closely related to viral infection and intestinal bacteria. However, little is known about bacteria within the HCC tumor microenvironment. Here, we showed that intratumoral Mycoplasma hyorhinis (M.

Erratum: Targeting myeloid-derived suppressor cells to attenuate vasculogenic mimicry and synergistically enhance the anti-tumor effect of PD-1 inhibitor.

[This corrects the article DOI: 10.1016/j.isci.

Biomimetic Immunosuppressive Exosomes that Inhibit Cytokine Storms Contribute to the Alleviation of Sepsis.

Sepsis is a disease characterized by multiple organ failure caused by immune hyperactivation and cytokine storms. Studies have shown that the incidence of sepsis in melanoma patients is substantially lower compared to the general population. It is also observed that experimental tumor-bearing animals have high survival rates after sepsis induction, suggesting that tumors may suppress sepsis-associated immune overactivation, thereby alleviating sepsis.

Pinin Induces Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma by Regulating m6A Modification.

Pinin is a moonlighting protein localized in desmosomes and nucleus. It could promote the growth of hepatocellular carcinoma. Whether this protein can induce epithelial-to-mesenchymal transition (EMT) and malignant progression in HCC is unknown.

Targeting myeloid-derived suppressor cells to attenuate vasculogenic mimicry and synergistically enhance the anti-tumor effect of PD-1 inhibitor.

Myeloid-derived suppressor cells (MDSCs) enhance the proliferation of endothelial cells to stimulate angiogenesis. However, many aggressive malignant tumors do not have endothelial cell-dependent blood vessels in the early stage and instead generate microcirculation by forming vasculogenic mimicry (VM). To date, the relationship between MDSCs and tumor cells remains the focus of ongoing studies.

RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway.

Vasculogenic mimicry (VM) formed by aggressive tumor cells to mimic vasculogenic networks plays an important role in the tumor malignancy of HCC. However, the pathogenesis underlying VM is complex and has not been fully defined. m6A is a common mRNA modification and has many biological effects.

Targeted Drug-Loaded Chemical Probe Staining Assay to Predict Therapy Response and Function as an Independent Pathological Marker.

Multi-targeted kinase inhibitors, such as sorafenib, have been used in various malignancies, but their efficacy in clinical applications varies among individuals and lacks pretherapeutic prediction measures. We applied the concept of "click chemistry" to pathological staining and established a drug-loaded probe staining assay. We stained the cells and different types of pathological sections and demonstrated that the assay was reliable.

USP5 promotes epithelial-mesenchymal transition by stabilizing SLUG in hepatocellular carcinoma.

The role of SLUG in epithelial-mesenchymal transition during tumor progression has been thoroughly studied, but its precise regulation remains poorly explored. The affinity purification, mass spectrometry and CO-IP were performed to identify the interaction between SLUG and ubiquitin-specific protease 5 (USP5). Cycloheximide chase assays and deubiquitination assays confirmed that the effect of USP5 on the deubiquitin of SLUG.

Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway.

Background: Hypoxia commonly occurs in solid tumors. The hypoxia in the center of solid tumors considerably decreases the chemosensitivity of tumor cells and induces epithelial-mesenchymal transition (EMT) as well as drug resistance of antitumor drugs.

Methods: Here, the effects of salidroside (Sal) combined with platinum drugs on human hepatocellular carcinoma were examined in vitro and in vivo.

Polyphyllin I suppresses the formation of vasculogenic mimicry via Twist1/VE-cadherin pathway.

Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells and is related to the metastasis and poor prognosis of many cancer types, including hepatocellular carcinoma (HCC). Thus far, no effective drugs have been developed to target VM. In this study, patients with liver cancer exhibited reduced VM in tumor tissues after treatment with Rhizoma Paridis.

Derepression of co-silenced tumor suppressor genes by nanoparticle-loaded circular ssDNA reduces tumor malignancy.

The co-silencing of multiple tumor suppressor genes can lead to escalated malignancy in cancer cells. Given the limited efficacy of anticancer therapies targeting single tumor suppressor genes, we developed small circular single-stranded DNA (CSSD) that can up-regulate the expression of co-silenced tumor suppressor genes by sequestering microRNAs (miRNAs) that negatively regulate these genes. We found that cancer patients with low tumor expression of the tumor suppressor genes , , and had shortened survival times.

Dihydroartemisinin inhibits EMT induced by platinum-based drugs via Akt-Snail pathway.

Artemisinin and its derivatives exhibit a high activity against a range of cancer cell types both and . In clinical practice, platinum-based anti-cancer chemotherapy is widely used to treat tumors. However, a large proportion of patients receiving these treatments will relapse because of metastasis and drug resistance.

Sesquiterpene binding Gly-Leu-Ser/Lys-"co-adaptation pocket" to inhibit lung cancer cell epithelial-mesenchymal transition.

Sesquiterpene lactones (SL) have a wide range of applications in anti-tumor and anti-inflammatory therapy. However, the pharmacological mechanism of such substances is not clear. In this study, parthenolide (PTL) was used as an example to explore the anti-tumor effect of natural molecules and their common mechanism.

Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma.

Background: Vascular endothelial growth factor receptors (VEGFRs) are the major receptors involved in endothelial cell-dependent tumor angiogenesis. There are studies account for the effects of Hsp90 on angiogenesis, but the role and mechanism of Hsp90β isoforms and NVP-BEP800, a specific inhibitor of Hsp90β, in tumor angiogenesis is rarely mentioned.

Methods: Immunohistochemistry and statistical analysis was used to evaluate the correlation between Hsp90β expression, CD31 endothelial cell-dependent vessel density, and VEGFRs expression in tissue samples of 96 HCCs.