Cervical squamous cell carcinoma (CSCC) is a type of female cancer that affects millions of families worldwide. Human papillomavirus (HPV) infection is the main reason for CSCC formation, and squamous intraepithelial lesions (SILs) induced by high-risk HPV (HR-HPV) infection are considered precancerous lesions. A previous study reported that HPV-infected cancer cells were able to counteract lipid peroxidation for survival. Recent research has reported that ferroptosis acts in an iron-dependent lipid peroxidation manner to kill cancer cells, and it is proposed as a new approach for female cancer therapy. Here, we investigated the role of ferroptosis throughout SIL development into CSCC. We found that ferroptosis occurred in SIL, but anti-ferroptosis emerged in CSCC. Our data further indicated that an antiferroptotic effect was formed in response to persistent ferroptosis and then promoted oncogenesis. Altogether, we provide novel insight into ferroptosis in cervical SIL development and suggest a potential therapeutic target for the treatment of CSCC.

Organ transplantation is the most promising curation for end-stage organ disease. However, the donor organ shortage has become a global problem that has limited the development of organ transplantation. Human-animal chimeras provide the ability to produce human organs in other species using autologous stem cells [e.g., induced pluripotent stem cells (iPSCs) or adult stem cells], which would be patient-specific and immune-matched for transplantation. Due to the potential application prospect of interspecies chimeras in basic and translational research, this technology has attracted much interest. This review focuses primarily on technological advances, including options of donor stem cell types and gene editing in donor cells and host animals, in addition to perspectives on human-animal chimeras in clinical and basic research.

Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC.

Cuproptosis is a newly defined regulated cell death model and is considered as a potential approach for cancer treatment. We have previously found that cervical cancer cells have the capability of anti-ferroptosis. A recent study has reported that elesclomol (ES) is able to induce copper-dependent ferroptosis. However, its effect on cervical cancer cell ferroptosis is still unclear. In this study, we found that the expression levels of copper metabolism-related genes ATP7A and ATP7B were decreased in cervical cancer tissues. In cervical cancer cells, combined treatment of ES and Cu²⁺ inhibited cell proliferation and promoted cell death, but did not promote cuproptosis. However, ES-Cu²⁺ treatment led to the accumulation of cellular reactive oxygen species, increased cellular Fe²⁺ levels, and decreased expression of GPX4. Moreover, the expression levels of HMOX1 and FTH1 were increased, while the expression level of TFRC was decreased after co-treated with ES-Cu²⁺ in cervical cancer cells. The decreased expression of GPX4 induced by ES-Cu²⁺ was attenuated by ferroptosis inhibitors ferrostatin-1 and DFO. Knockdown of HMOX1 could alleviate ES-Cu²⁺-induced GPX4 downregulation. The expression level of HMOX1 was upregulated in cervical cancer tissues and was negatively associated with ATP7B. In conclusion, copper metabolism is altered in cervical cancer tissues. ES-Cu²⁺ co-treatment induce ferroptosis in cervical cancer cells by upregulating HMOX1. Our study provides new insights into the relation between cuproptosis and ferroptosis, which may be potential for clinical therapies of cervical cancer.

This article is aimed at exploring the relationship between the phosphatase 2A catalytic subunit Cα (PP2Acα, encoded by PPP2CA) and methyltransferase‐like 3 (METTL3) in the malignant progression of gastric cancer (GC). Through analyzing the bioinformatics database and clinical tissue immunohistochemistry results, we found that abnormal PP2Acα and METTL3 levels were closely related to the malignant progression of GC. To explore the internal connection between PP2Acα and METTL3 in the progression of GC, we carried out cellular and molecular experiments and finally proved that PP2Acα inhibition can upregulate METTL3 levels by activating ATM activity, thereby promoting the malignant progression of GC.