Journal of Environmental Pathology, Toxicology and Oncology

Microplastics and Cancer: A Comprehensive Review of Their Impact on Tumor Progression and Mechanisms of Carcinogenesis

Microplastics (MPs), pervasive environmental pollutants, have raised significant concerns regarding their potential impact on human health, particularly in relation to cancer. This review examines the current evidence linking MPs to various cancers, including ovarian, gastric, blood, brain, colorectal, lung, liver, breast, and cervical cancers. Recent studies indicate that MPs, including polystyrene nanoparticles (PS-NPs) and microplastics (PS-MPs), can exacerbate tumor progression through mechanisms such as oxidative stress, inflammation, and endocrine disruption. For instance, in ovarian cancer, PS-NP exposure has been shown to accelerate tumor growth, while in gastric cancer, PS-MPs alter gene expression to promote cancer progression. Blood cancer research highlights the presence of MPs in human blood, suggesting their potential systemic distribution and impact. MPs' ability to cross the blood-brain barrier raises concerns about brain cancer, where they may induce neurotoxicity. Similarly, MPs contribute to colorectal cancer by causing intestinal inflammation and gut microbiota alterations. Inhalation of MPs is linked to lung cancer due to chronic inflammation and oxidative stress. In liver cancer, MPs induce hepatic toxicity and promote carcinogenesis. Breast and cervical cancers are associated with MPs endocrine-disrupting properties, leading to increased cell proliferation and migration. This review underscores the urgent need for further research to elucidate the mechanisms through which MPs contribute to cancer and to inform public health strategies and regulatory policies aimed at mitigating the risks of microplastic exposure.

Effects of RNA Modification "Writers" of GALNT2 on the Tumor Microenvironment in Cervical Squamous Cell Carcinoma

Cervical squamous cell carcinoma (CESC) is one of the most common causes of cancer-related deaths in women. RNA modification "writers" modulate and alter RNA molecular activity and have been implicated in the origin and development of cancer. We explored the effects of RNA modification writers on the tumor microenvironment in CESC and their prognostic value. RNA modification writers were altered at the genetic and transcriptional levels in CESC sample data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. A principal component analysis (PCA) score model was established based on the genes screened by Cox regression analysis and random forest dimensionality reduction. A survival analysis of CESC patients revealed significant differences between patients with high and low scores. The gene set variation analysis method was used for a functional enrichment analysis. The relative abundance of immune cells in CESCs was quantified using the CIBERSORT algorithm. There were significant differences in multiple signaling pathways and immune cells between the patients with high and low scores. Based on Genomics of Drug Sensitivity in Cancer data, we analyzed the genetic mutations in CESCs and predicted the therapeutic effects of multiple anticancer drugs. Patients with high scores showed significant resistance. Finally, the N-acetylgalactosaminyltransferase 2 (GALNT2) was highly expressed in CESCs and was associated with multiple immune cells and the formation of the extracellular matrix. PCA score based on RNA modification writers is closely associated with immune infiltration in the tumor microenvironment and could be used as a reference for prognosis and medication in CESC patients.

Molecular Mechanism of Long Non-Coding RNAs in Ovarian Cancer: CASC19 Regulates the Malignant Progression of Ovarian Cancer through miR-761/CBX2 Axis

Long non-coding RNAs (lncRNAs) are involved in the numerous types of tumors. The aim of this study is to comprehend the pathological mechanism of lncRNA CASC19 in ovarian cancer. CASC19, miR-761 and CBX2 expression in the samples was quantitatively detected by real-time quantitative polymerase chain reaction (RT-qPCR) reaction. The proliferation and apoptosis levels of ovarian cancer cells were evaluated via cell counting kit-8 (CCK-8) and Flow cytometry assays. The targeting relationship and correlation of CASC19, miR-761 and CBX2 were investigated through luciferase reporter assay and Pearson assay. CASC19 and CBX2 were enriched in ovarian cancer, while miR-761 expression was decreased. Silencing CASC19 suppressed the cell growth and promoted cell apoptosis. CASC19 targeted the inhibition of miR-761 expression and regulated the level of CBX2. In addition, the miR-761 inhibitor reversed the inhibitory effect of si-CASC19 on the biological activity of ovarian cancer cells, while si-CBX2 restored the regulation of miR-761 inhibitor on the development of ovarian cancer. lncRNA CASC19 mediated the malignant progression of ovarian cancer through miR-761/CBX2 axis, which provided a potential therapeutic target for the cure of patients.

HIF-1α Activates Hypoxia-Induced MXRA5 Expression in the Progression of Ovarian Cancer

The hypoxic microenvironment of tumor cells is closely related to the progression of ovarian cancer (OV). Hypoxia (HY)-related matrix-remodeling associated 5 (<i>MXRA5</i>) was expressed at elevated levels in many tumors, but research on the impact of <i>MXRA5</i> in OV remains limited. This study aims to explore the role of <i>MXRA5</i> in regulating cellular HY in OV. The <i>MXRA5</i> expression and its clinical significance in OV were evaluated using GEPIA2, Kaplan-Meier plotter databases, and immunohistochemistry assay. OV cells were treated with normoxia and HY conditions. The siRNAs were designed to knock down the <i>MXRA5</i> expression in hypoxic cells. The cellular capacities were detected by CCK-8 assay, EdU assay, Transwel assay, and TUNEL assay, each method targeting a different aspect of cellular behavior. The <i>MXRA5</i> level was increased in OV and associated with the progression free survival and overall survival of OV patients. The proliferation and invasion abilities of OV cells were promoted, while apoptosis capacities were inhibited in hypoxic cells. After the knockdown of <i>MXRA5</i> in hypoxic cells, the proliferative capacities and invasive abilities of the cells were reduced, and the apoptosis capacities were enhanced. Moreover, mechanistically, HIF-1α is a key transcription factor in response to HY that binds to the <i>MXRA5</i> promoter. <i>MXRA5</i> expression was induced by HY and had prognostic performance in OV. Knockdown of <i>MXRA5 </i>can inhibit proliferation and invasion in OV cells caused by HIF-1α, revealing that <i>MXRA5</i> is one potential targets for tumor HY regulation in OV

PFKFB3 Regulates the Growth and Migration of Ovarian Cancer Cells through Pyroptosis and Warburg Effect Progression

Ovarian cancer is one of the most common malignant tumors in female reproductive organs. Its incidence rate is second only to uterine body cancer and cervical cancer, posing a serious threat to women's health. Herein, we explored that <i>PFKFB3</i> in cancer progression of ovarian cancer and its underlying mechanism. All the serum samples from ovarian cancer were collected by our hospital. <i>PFKFB3</i> mRNA expressions in patients with ovarian cancer and ovarian cancer cell lines were up-regulated. <i>PFKFB3</i> protein expressions in ovarian cancer cells were induced. ovarian cancer patients with high <i>PFKFB3</i>expression had lower survival rate. The <i>PFKFB3</i>gene promoted cell proliferation and EDU cells, and increased cell metastasis of ovarian cancer. Si-<i>PFKFB3</i> reduced cell proliferation and EDU cells, and decreased cell metastasis of ovarian cancer. <i>PFKFB3</i> gene up-regulation reduced caspase-3/9 activity levels of ovarian cancer. Si-<i>PFKFB3</i> also promoted caspase-3/9 activity levels of ovarian cancer. <i>PFKFB3</i> gene promoted Warburg effect progression of ovarian cancer. <i>PFKFB3</i> gene reduced NLRP3-induced pyroptosis of ovarian cancer. <i>PFKFB3</i> suppressed NLRP3 expression. NLRP3 was one target spot for <i>PFKFB3</i> on pyroptosis of ovarian cancer. Taken together, we conclude that <i>PFKFB3</i> suppressed NLRP3 axis to reduce pyroptosis and increase Warburg effect progression of ovarian cancer, and provide molecular insight into the mechanisms by which the <i>PFKFB3</i> regulates pyroptosis of ovarian cancer.

Construction and Characterization of Cadherin 6 (CDH6)-Targeting Chimeric Antigen Receptor (CAR) Modified T Cells

In this study, we constructed cadherin 6 (CDH6)-targeting chimeric antigen receptor (CAR) modified T cells (CAR-T cells) and investigated their target-specific recognition and tumor-specific cytocidal effect through in vitro approach. CDH6 expression at the transcriptional level and its correlation with clinicopathological parameters in various tumor types were analyzed using online bioinformatics tool. Conventional molecular cloning method was used to construct the lentiviral vector encoding CDH6-specific CAR and the lentivirus was prepared using 3-plasmid transient cotransfection method. CDH6-targeting CAR-T cells were prepared using centrifugal infection method, and the specific recognition and cytocidal effects of CAR-T cell targets were investigated through in vitro co-culture experiments. At the transcription level, CDH6 was significantly overexpressed in ovarian cancer tissues (P < 0.05). Although it was not correlated with tumor stage and patient's prognosis, the overexpression of CDH6 was positively associated with the expression of paired-box 8 (PAX8), a lineage-specific transcription factor. In the present study, we successfully established CDH6-targeting CAR-T cells that can secrete effector cytokines and produce specific cytocidal effects after being co-cultured with CDH6-positive ovarian cancer cells in vitro. Thus, CDH6, as a lineage-specific factor of ovarian tissue, may be an ideal target for CAR-T cell therapy of ovarian cancer.

Deciphering the Role of Human Gastrointestinal Microbiota in the Pathogenesis of Vaginal Infection and Cervical Cancer

The human microbiota typically contains symbionts and supports the host, although it can be commensal or reciprocal and pathogenic in its host function, immunity, and diet. Modern studies indicate that perturbations in the microbiome may be present in quite a few diseases, including inflammation and cancer. To be more specific, changes in the microbiomes of the gut and vagina may be related to various gynecologic cancers (cervical, uterine, and ovarian). Furthermore, the gastrointestinal microbiota can be altered by environmental factors and pre-existing morbidities and may cause nausea, vomiting, diarrhea, constipation, bloating, and abdominal pain. A healthy female gut microbiome is dominated by Bifidobacterium, Lactobacillus, Bacteroides, Clostridium, Escherichia, Streptococcus, and Ruminococcus; the vaginal microbiome includes Firmicutes, specifically Lactobacilli spp. However, the gram-variable coccobacillus Gardnerella vaginalis (previously known as Haemophilus vaginalis) dominates the microbiota of biological vaginosis (BV) and includes several anaerobic organisms. Vaginal microbiota perturbations can cause vaginal pain, sexual dysfunction, and urinary symptoms. In the current review paper, we explore recent research along with existing gaps in knowledge related to the association of changes in microbiota diversity and the pathogenesis of vaginal infection-associated cervical cancer.