Iranian Journal of Allergy, Asthma and Immunology

Investigating Novel Biomarkers in Endometrial Cancer: A Study on RT-qPCR and Immunohistochemistry

This study aimed to investigate the expression patterns of HOXB9, DLX5, NGR1, and GATA6 in endometrial cancer tissues compared to adjacent non-cancerous tissues. Using RT-qPCR and immunohistochemistry, the researchers found significant upregulation of HOXB9, DLX5, and NGR1, and downregulation of GATA6 in endometrial cancer samples. The biomarker expression levels correlated with clinicopathological features, and survival analysis revealed that high expression of HOXB9, DLX5, and NGR1 was associated with poorer prognosis, while high GATA6 expression indicated better outcomes. These findings suggest that these biomarkers may play crucial roles in endometrial cancer development and progression, highlighting their potential as diagnostic, prognostic, and therapeutic targets.

MiR-425-5p Mediation of Malignant Behavior and Immune Escape of Cervical Cancer Cells by Targeting NCAM1

MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells. The levels of neural cell adhesion molecule 1 (NCAM1) and miR-425-5p in CxCa tissues and cells were tested using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests. CxCa cells’ malignant phenotype was examined through clone formation tests, and transwell tests. CD8+T cells were co-cultured with CxCa cells and then analyzed for apoptosis rates and the expression of activation proteins (granzyme B (GZMB) and perforin) as well as immune factors (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) using flow cytometry, western blot, and enzyme-linked immunosorbent assay (ELISA) methods. Finally, in nude mouse experiments, the tumor size was measured for subcutaneous tumors, and the expression of CD8+T cell-related factors was detected. The NCAM1 and miR-425-5p were down-regulated and up-regulated in CxCa tissue and cells, respectively. After silencing miR-425-5p, CxCa cells showed attenuation in vitality, clone formation rate, and their capacities to migrate, penetrate, and evade immune responses. NCAM1 was targeted and silenced by miR-425-5p. When NCAM1 was silenced, it partially counteracted miR-425-5p’s inhibitory effects on the immune escape and proliferation. In nude mice, the tumor size and weight decreased after silencing miR-425-5p, and levels of CD8, IFN-γ, TNF-α, perforin, and GZMB were elevated. However, these changes were reversed when NCAM1 was silenced. In conclusion, miR-425-5p mediates the biological behavior and immune evasion of CxCa cells by regulating NCAM1.

Ellagic Acid Ameliorates Ovarian Cancer via Modification of Pyroptosis and Inflammation

Ovarian cancer is 1 of the most serious female malignancies worldwide. Despite intensive efforts to overcome ovarian cancer, there remain limited treatment options for this disease. Ellagic acid (EA), a well-known phytochemical with anti-inflammatory properties, is suggested as a therapeutical strategy as it can inhibit the growth of certain cancer cells. However, its effect on human ovarian carcinoma cells has not yet been fully elucidated. The present study aimed to explore the effect of EA on ovarian carcinoma and further expound the underlying mechanisms of EA-induced ovarian cancer cell death. Human ovarian carcinoma cell lines, A2780 and OVCAR3, were treated with EA (0, 10, 20, 50, and 100 μM) and assessed for viability, cell cycle (cyclin D1 and cyclin E), pyroptosis (gasdermin D [GSDMD] and gasdermin E [GSDME]), autophagy (microtubule-associated protein 1A/1B-light chain 3 [MAP1LC3] and autophagy protein 5 [ATG5]), and inflammation (interleukin [IL]-1b and IL-6) via 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA). The findings showed that EA could significantly inhibit cell viability, decrease cyclin D1 and E levels, downregulate GSDMD and GSDME, and suppress the levels of inflammatory markers, including IL-1b and IL-6. However, the protein levels of autophagic markers including LC3 and ATG5 remained mostly unchanged. The findings suggest that EA could suppress ovarian cancer cell viability and proliferation by arresting both cell lines at the G1 phase of the cell cycle through modification of cell death mediated by inflammatory-caused pyroptosis.

Association between HLA-DRB1.2 Genotypic Diversity and Cervical Cancer in Women Infected with the Human Papillomavirus

Cervical cancer is a significant public health concern, particularly in women infected with the human papillomavirus (HPV). Recent evidence suggests that host genetic factors, specifically those related to the human leukocyte antigen (HLA) system, may also play a crucial role in determining susceptibility to cervical cancer in HPV-infected individuals. In this study, 86 patients with HPV and 27 healthy donors were selected from May 2023 to February 2024. HLA-DRB1 genotypes were determined using polymerase chain reaction followed by high-resolution melting curve analysis (HRM). Genotype frequencies in patients were compared with those in the control group from donors. Based on the HRM analysis, 10 genotypes were found in both patients and controls (profiles A-J). In the analysis of HLA-DRB1 genotypes, C, F, and I showed significant associations with HPV infection, indicating a possible protective effect against infection. Notably, genotype B was strongly linked to high-risk HPV, while genotype A was associated with low-risk HPV and is relevant to infection history. However, the remaining genotypes examined in the study did not exhibit significant associations with the analyzed parameters. This study contributes valuable evidence regarding the role of HLA-DRB1 genotypes in cervical cancer susceptibility and highlights the potential clinical implications for risk assessment and targeted immunotherapies. The use of HRM for HLA typing offers advantages that are efficient, accurate, and scalable, making it suitable for large-scale studies and clinical applications.

Bioinformatics-driven Identification of lncRNA LINC02381 in Mediating Cisplatin Resistance via IL-12 Induced Wnt/TCF7 Signaling in Ovarian Cancer

Cisplatin resistance presents a considerable hurdle in the treatment of ovarian cancer, significantly impacting patient outcomes and limiting the effectiveness of chemotherapy. This study employs advanced bioinformatics techniques-including RNA sequencing (RNA-seq), DNA sequencing (DNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq)-to elucidate the molecular mechanisms underlying this resistance, with a particular focus on the long non-coding RNA (lncRNA) LINC02381. Our findings reveal that LINC02381 is significantly upregulated in ovarian cancer cells exhibiting resistance to cisplatin, suggesting its pivotal role in mediating this phenomenon. We further demonstrate that cytokines, particularly interleukin-12 (IL-12), secreted by immune cells within the tumor microenvironment, activate the Wnt signaling pathway. This activation leads to the binding of the transcription factor TCF7 to the promoter region of LINC02381, resulting in enhanced expression of this lncRNA. Notably, this interaction establishes a positive feedback loop in which LINC02381 not only promotes its own expression but also amplifies Wnt signaling activity. This cascade ultimately drives the upregulation of ATP-binding cassette (ABC) transporters, which are crucial for the efflux of cisplatin from cancer cells. Thus, the drug's intracellular concentration is reduced, and cell survival under chemotherapy pressure is facilitated. These insights uncover a novel mechanism of cisplatin resistance driven by the IL-12/Wnt/TCF7/LINC02381 axis, highlighting the complex interplay between immune signaling and drug resistance in ovarian cancer. Our findings suggest that targeting this regulatory pathway may offer promising therapeutic strategies to overcome chemotherapy resistance, paving the way for improved treatment outcomes in patients with ovarian cancer. Future research should focus on validating these mechanisms and exploring potential interventions that disrupt this feedback loop.

Research Progress of Immune Mechanisms Related to Persistent HPV Infection in CIN after Cervical Conization

Persistent human papillomavirus (HPV) infection is associated with the grading of cervicalintraepithelial neoplasia (CIN), high-risk HPV infection, multiple HPV infections, high HPV load,HPV infection of surgical margin, and age in CIN after conization. The immune mechanism iscomplex and is primarily related to vaginal microecology disorders, immune escape, immuneresponse impairment, and the release of regulatory cytokines. Currently, the treatment methods forpostoperative persistent HPV infection include surgical treatment, antiviral treatment, vaccination,and other approaches.

Astragalus Polysaccharide Mediates Immunomodulatory Effects on Crosstalk between Human Peripheral Blood Mononuclear Cells and Ovarian Cancer Cell Line

Astragalus polysaccharide (APS) is a functional component of Astragalus membranaceus with antitumor and immunomodulatory properties. This study evaluated the effect of APS on the peripheral blood mononuclear cell (PBMC) proliferation, cytokine secretion, and regulatory T cell (Treg) induction in an in vitro coculture model of human PBMCs and A2780 human ovarian cancer cells. PBMC proliferation and Treg frequency were measured by flow cytometry. Cytokine levels were assessed by enzyme-linked immunosorbent assay. APS significantly enhanced the PBMC proliferation, reduced Treg frequency, decreased anti-inflammatory cytokines including interleukin [IL]-10, transforming growth factor beta (TGF-β), and vascular endothelial growth factor-A (VEGF-A), and increased the pro-inflammatory cytokine IL-6. These findings suggest that APS may be an effective immunomodulatory supplement for cancer therapy, particularly for ovarian cancer by enhancing antitumor immune responses.

The Role of LINC02381 in Modulating Cisplatin Resistance in Ovarian Cancer: A Bioinformatics Approach

Cisplatin resistance presents a significant challenge in cancer therapy, emphasizing the necessity for identifying new regulatory elements that influence drug response. Recent research has revealed the importance of long noncoding RNAs (lncRNAs) in chemotherapy resistance, with LINC02381 identified as a potential regulatory factor. Through an in-depth bioinformatics analysis, we investigated the impact of LINC02381 on cisplatin resistance in ovarian cancer across various datasets. By conducting differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and constructing protein-protein interaction (PPI) networks, we identified key pathways associated with LINC02381 expression. The results indicated that the altered expression of LINC02381 in patients treated with cisplatin was associated with reduced survival. Functional studies and correlation analyses further demonstrated that this LncRNA influences critical pathways and genes related to apoptosis, efflux, DNA repair, and EMT. Lastly, through an examination of its interactions with microRNA and protein networks, we identified LINC02381 as a ceRNA implicated in cisplatin resistance. Our findings suggest that LINC02381 may influence cisplatin sensitivity in ovarian cancer and establish a basis for further experimental validation, including molecular assays or in vivo analyses, and suggest the potential therapeutic targeting of LINC02381 to combat chemoresistance.