Ferroptosis is a type of cell death that depends on iron and reactive oxygen species (ROS). The accumulation of iron and lipid peroxidation primarily initiates oxidative membrane damage during ferroptosis. The core molecular mechanism of ferroptosis includes the regulation of oxidation and the balance between damage and antioxidant defense. Tumor cells usually contain a large amount of H₂O₂, and ferrous/iron ions will react with excessive H₂O₂ in cells to produce hydroxyl radicals and induce ferroptosis in tumor cells. Here, we reviewed the latest studies on the regulation of ferroptosis in tumor cells and introduced the tumor-related signaling pathways of ferroptosis. We paid particular attention to the role of noncoding RNA, nanomaterials, the role of drugs, and targeted treatment using ferroptosis drugs for mediating the ferroptosis process in tumor cells. Finally, we discussed the currently unresolved problems and future research directions for ferroptosis in tumor cells and the prospects of this emerging field. Therefore, we have attempted to provide a reference for further understanding of the pathogenesis of ferroptosis and proposed new targets for cancer treatment.

In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.

There is increasing evidence that long non-coding RNAs (lncRNAs) play important roles in human tumorigenesis. By using publicly available expression profiling data from lung adenocarcinoma and integrating bioinformatics analysis, we screened a lncRNA, LINC00472. LINC00472 expression in lung adenocarcinoma tissues was significantly lower and tightly associated with patient prognosis and TNM clinical stages in lung adenocarcinoma. LINC00472 also inhibited lung adenocarcinoma cell migration and invasion and increased cell stiffness and adhesion. RNA pull down and RIP assays identified that LINC00472 interacted with the transcription factor Y-box binding protein 1 (YBX1), which partially reversed the inhibition of cell migration and invasion and increased LINC00472-induced cell stiffness and adhesion. LINC00472 also regulated the density and integrity of F-actin in A549 and PC-9 cells possibly via YBX1. LINC00472 inhibited the cell epithelial-mesenchymal transition (EMT) processes via the modulation of YBX1. These results indicated that LINC00472 inhibited the cell EMT process by binding to YBX1, and affected the mechanical properties of the cell, ultimately inhibited its ability to invade and metastasize. Collectively, the present study provides the first evidence that LINC00472 changes the mechanical properties and inhibits the invasion and metastasis of lung adenocarcinoma cells.

Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues. The correlation between AFAP1-AS1 and the clinicopathological features was evaluated using the chi-square test. The effects of AFAP1-AS1 on TSCC cells were determined via a CCK-8 assay, clone formation assay, flow cytometry, wound healing assay and transwell assay. Furthermore, the effect of AFAP1-AS1 knockdown on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, CAL-27 cells with AFAP1-AS1 knockdown were subcutaneously injected into nude mice to evaluate the effect of AFAP1-AS1 on tumor growth in vivo. In this study, we found that lncRNA AFAP1-AS1 was increased in TSCC tissues and that patients with high AFAP1-AS1 expression had a shorter overall survival. Short hairpin RNA (shRNA)-mediated AFAP1-AS1 knockdown significantly decreased the proliferation of TSCC cells. Furthermore, AFAP1-AS1 silencing partly inhibited cell migration and invasion. Inhibition of AFAP1-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of EMT-related genes (SLUG, SNAIL1, VIM, CADN, ZEB1, ZEB2, SMAD2 and TWIST1) in TSCC cells. In addition, CAL-27 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on tumorigenesis in vivo. Downregulation of AFAP1-AS1 suppressed tumor growth and inhibited the expression of EMT-related genes (SLUG, SNIAL1, VIM, ZEB1, NANOG, SMAD2, NESTIN and SOX2) in vivo. Taken together, our findings present a road map for targeting the newly identified lncRNA AFAP1-AS1 to suppress TSCC progression, and these results elucidate a novel potential therapeutic strategy for TSCC.

Long non-coding RNAs (lncRNAs) are dysregulated in various cancers. However, the clinical relevance and functional roles of AFAP1-AS1 in colon cancer (CC) have not been clarified. We analyzed the lncRNA expression patterns in Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) RNA-seq datasets, and found that the expression level of AFAP1-AS1 was significantly elevated in CC tissues. High levels of AFAP1-AS1 were associated with poor disease-free survival and overall survival in CC patients. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the cell invasive and migration capability in CC cell line HT-29. AFAP1-AS1 knockdown also increased the expression of E-cadherin and ZO-1 while inhibited the expression of Vimentin, MMP9, ZEB1 and β-catenin, suggesting that AFAP1-AS1 is involved in the epithelial-mesenchymal transition (EMT) process of CC. Further studies confirmed that AFAP1-AS1 knockdown also affected the actin-cytokeratin signaling pathway. Thus, AFAP1-AS1 might be a potential novel diagnostic marker and therapeutic target for CC.

Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8⁺ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.