Neoplasma最新文献

{"title":"EIF4E promotes gefitinib resistance in non-small cell lung cancer by activating the Wnt/β-catenin pathway.","authors":"Bo Zhang, Jiani Zhu, Zixian Jin, Jiawei Liang, Ziming Wang, Quanteng Hu, Lilong Xia","doi":"10.4149/neo_2025_250113N19","DOIUrl":"10.4149/neo_2025_250113N19","url":null,"abstract":"<p><p>Tyrosine kinase inhibitors (TKIs) like gefitinib, which target the epidermal growth factor receptor (EGFR), show considerable therapeutic effectiveness in non-small cell lung cancer (NSCLC) with EGFR-activating mutations. Nevertheless, the resistance that develops against EGFR-TKIs diminishes their therapeutic impact in clinical settings. This investigation focused on the impact of eukaryotic translation initiation factor 4E (eIF4E) on gefitinib resistance in NSCLC. Using the CCK-8 assay, the influence of different gefitinib concentrations on cell proliferation was examined. eIF4E and EGFR expressions were verified by qRT-PCR and/or western blotting in NSCLC cell lines. Moreover, the effects of eIF4E knockdown in gefitinib-treated PC9/GR cells were detected by CCK-8, flow cytometry, colony formation assays, and xenograft tumor model. eIF4E expression was remarkably upregulated in the gefitinib-resistant PC9/GR cells. Moreover, the expression levels of eIF4E in NSCLC cell lines exhibited a dose-dependent increase following gefitinib administration. The function assays demonstrated that reducing eIF4E levels hindered the proliferation of PC9/GR cells and enhanced the apoptosis-inducing effects of gefitinib both in vitro and in vivo, and also had an inhibitory action on the Wnt/β-catenin pathway. Taken together, these results suggested that eIF4E confers gefitinib resistance in NSCLC by regulating the Wnt/β-catenin pathway. Therefore, eIF4E is a possible therapeutic target for improving therapeutic action in NSCLC patients who have developed resistance to gefitinib.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"72 1-2","pages":"118-127"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated expression of HSF1 promotes the progression of colorectal cancer by activating CLDN3 transcription.","authors":"Yanxi Shao, Ting Ma, Dening Ma, Lue Hong, Min Lv, Shiqi Zhou, Zhibin Fang, Enyan Yu, Xia Li, Yuping Zhu","doi":"10.4149/neo_2025_241031N442","DOIUrl":"10.4149/neo_2025_241031N442","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with increasing morbidity and mortality. Heat shock transcription factor 1 (HSF1), as an important transcription factor regulating the expression of heat shock proteins, has been proven to play a crucial role in the development of various tumors. Yet the potential mechanism and clinical significance of HSF1 in CRC remain unclear and require further exploration. We used TCGA database to understand the clinical significance of HSF1 in CRC. Then, we verified the expression of HSF1 in CRC tissues by immunohistochemistry and analyzed its clinical significance. By constructing stable knockdown and overexpressed of HSF1 in cell lines to investigate the potential mechanisms of HSF1 to regulate CRC cell proliferation, migration, and invasion in vivo and in vitro. Next, differential genes expressed by HSF1 in CRC were analyzed by bioinformatics technology, and their correlation and interaction were verified by PCR, WB, and CHIP experiments. We confirmed that HSF1 is highly expressed in CRC and its upregulation is associated with poor prognosis of malignant events in CRC. Functionally, HSF1 can enhance the proliferation, invasion, and migration of CRC cell lines. In vivo experiments have shown that knockdown of HSF1 can inhibit tumor growth. In terms of molecular mechanism, we found that HSF1 can directly bind to the transcription factor binding site of CLDN3 and activate its transcription. Our research demonstrates the clinical significance and carcinogenic effect of HSF1. The functional mechanisms of HSF1 and its targets may serve as diagnostic and therapeutic targets for CRC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"67-79"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear factor I-C aggravates acute myelogenous leukemia by inhibiting SRY-box transcription factor 1 to activate autophagy.","authors":"Cong Luo, Zeyu Luo, Junjun Li, Feng Wen, Yixiong Cao, Qiong Liu, Xingxing Long","doi":"10.4149/neo_2025_240905N376","DOIUrl":"10.4149/neo_2025_240905N376","url":null,"abstract":"<p><p>Despite advances in chemoradiotherapy and hematopoietic stem cell transplantation, the treatment of acute myeloid leukemia (AML) remains challenging due to significant side effects and poor prognosis. This study aimed to investigate the role of nuclear factor I-C (NFIC) in AML progression by evaluating whether NFIC exacerbates AML through the inhibition of SRY-box transcription factor 1 (SOX1) and activation of autophagy, thereby providing potential insights for clinical treatment. NFIC and SOX1 expression levels in AML and normal samples were analyzed using bioinformatics, ELISA, RT-qPCR, and western blotting, and the interaction between NFIC and SOX1 was assessed through RNA pull-down and RNA-binding protein immunoprecipitation assays. Moreover, CCK-8 assay, FITC/PI apoptosis detection, immunofluorescence staining, RT-qPCR, and western blotting were conducted to assess cell viability, apoptosis, and the expression of NFIC, SOX1, Bax, Bcl-2, LC3-I, LC3-II, p62, and Beclin-1 following gene transfection. NFIC expression was significantly upregulated in AML samples while SOX1 expression was downregulated compared to normal controls. High NFIC levels were associated with poor prognosis in AML patients, and it was found to regulate SOX1 expression in KG-1 and NB4 cells negatively. Silencing NFIC or overexpressing SOX1 resulted in reduced cell viability and autophagy, and increased apoptosis in KG-1 and NB4 cells. Importantly, NFIC knockdown did not affect apoptosis in bone marrow mononuclear cells. The adverse effects of NFIC overexpression were reversed by SOX1 overexpression, highlighting the interplay between these factors in AML. This study demonstrates that NFIC promotes AML progression by activating autophagy and suppressing apoptosis in KG-1 and NB4 cells by inhibiting SOX1, providing a potential basis for therapeutic strategies targeting NFIC and SOX1 in AML.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"25-35"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of enzymatic activity of HRD1 results in death of cells derived from glioblastoma multiforme, neuroblastoma, and normal astrocytes.","authors":"Jaroslava Guzikova, Monika Liskova, Lubos Hudak, Maria Brodnanova, Andrea Evinova, Jozef Hatok, Peter Racay","doi":"10.4149/neo_2025_241120N481","DOIUrl":"10.4149/neo_2025_241120N481","url":null,"abstract":"<p><p>The aim of the present study was to examine the impact of LS-102, an inhibitor of enzymatic activity of HRD1 that is an essential E3 ubiquitin ligase of endoplasmic reticulum associated degradation (ERAD) on survival of the human cell lines derived from glioblastoma multiforme (GBM), neuroblastoma, and astrocytes. We have also examined molecular responses to HRD1 inhibition with a focus on proteins playing an essential role in unfolded protein response (UPR) and ERAD. In addition, activation of IRE1α documented by XBP1 splicing was investigated. Finally, we have examined the impact of LS-102 on p53 expression in GBM cells. Inhibition of HRD1 enzymatic activity results in cell death of all tested cells. With respect to GBM cells, U87 cells are more sensitive to LS-102 as T98G cells. Cells of cell lines derived from normal astrocytes K1884 exhibit the highest sensitivity to LS-102 among all cell types used in the study while NHA cells are the most resistant. Sensitivity of neuroblastoma SH-SY5Y cells to LS-102 is comparable to the sensitivity of U87 cells. In GBM cells, inhibition of HRD1 results in induction of the expression of proteins playing an essential role in UPR and ERAD (HRD1, SEL1L, and GRP78). XBP1 splicing induced by HRD1 inhibition was documented in T98G and K1884 cells. We did not observe induction of p53 expression in U87 cells. Since LS-102 induces cell death of normal astrocytes, it is not a candidate for the testing of its potential use as an antitumor treatment of GBM.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"16-24"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20(S)-ginsenoside Rg3 induced the necroptosis of prostate cancer cells via ROS overproduction.","authors":"Yanfei Peng, Yaping Guo, Shuwu Zhao, Hao Yan, Zheng Hao, Fang Zheng, Zhaiyi Zhang, Lin Miao, Li-Kang Sun, Muriel Cuendet","doi":"10.4149/neo_2025_240925N402","DOIUrl":"10.4149/neo_2025_240925N402","url":null,"abstract":"<p><p>Necroptosis is a programmed form of necrosis, and compounds inducing necroptosis may contribute to cancer treatment. 20(S)-ginsenoside Rg3 is a natural compound extracted from ginseng, which exhibited a broad-spectrum of antitumor activity. In the present study, the potential role of 20(S)-ginsenoside Rg3 in inducing necroptosis in prostate cancer cells was evaluated. 20(S)-ginsenoside Rg3 inhibited the proliferation of prostate cancer cells and upregulated the expression of necroptotic proteins such as receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, and their downstream mixed lineage kinase domain-like protein (MLKL). Pretreatment with the selective RIPK1 inhibitor necrostatin-1 (Nec-1) partially reversed the inhibitory effect of 20(S)-ginsenoside Rg3 on prostate cancer cell proliferation. 20(S)-ginsenoside Rg3 led to the accumulation of reactive oxygen species (ROS) and the regulation of autophagy in cancer cells. Scavenging ROS with N-acetyl-L-cysteine (NAC) antagonized the regulatory effects of 20(S)-ginsenoside Rg3 on cell autophagy and necroptotic proteins expression. Moreover, 20(S)-ginsenoside Rg3 exhibited an antitumor effect in a prostate cancer xenograft mouse model in which it upregulated the expression of RIPK1, RIPK3, MLKL and led to a decrease in tumor weight, as well as an increase in necrotic areas in tumor tissue. In conclusion, our study showed that 20(S)-ginsenoside Rg3 might induce necroptosis in prostate cancer in vitro and in vivo via the ROS/autophagy signaling pathway.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"48-58"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical experience and safety of venetoclax in the treatment of patients with chronic lymphocytic leukemia - real-world data from a hemato-oncology center.","authors":"Juliana Holasová, Alexander Wild, Mikuláš Hrubiško","doi":"10.4149/neo_2025_241211N518","DOIUrl":"10.4149/neo_2025_241211N518","url":null,"abstract":"<p><p>The treatment of patients with CLL has undergone significant changes in recent years. Standard chemoimmunotherapy is changing to targeted inhibition with modern drugs. The listed drugs have better efficacy and significantly improve the overall survival of patients according to registry clinical studies. In a retrospective analysis, we evaluated 43 patients with CLL who underwent venetoclax treatment at the Hematology Department, University Hospital and Polyclinic F. D. Roosevelt Banská Bystrica, Slovakia (FNsP FDR BB) in 2019-2024. The aim of this work was to evaluate retrospectively the efficacy and safety of venetoclax in the treatment of patients with CLL. The median age of patients at the time of initiation of venetoclax treatment was 58 years, range 41-79 years. The majority of patients, 27 (63%) were men and 16 (37%) were women. Patients were treated with venetoclax in the first and higher line, in combination with obinutuzumab, with rituximab, and in monotherapy. Of these, 16 (37%) patients were after previous treatment with ibrutinib. Treatment indications and response assessment were based on the 2018 international workshop on the Chronic Lymphocytic Leukemia (iwCLL) Criteria. Patients were evaluated after at least 2 months of treatment until disease progression. The effect of treatment was assessed by objective examination of the patient, possibly by imaging examination (USG, CT scan) and evaluation of blood parameters. Adverse effects were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. In case of disease progression, treatment was interrupted. The results of our work confirmed the efficacy and safety of venetoclax in combination with obinutuzumab, and rituximab, even as monotherapy in patients with CLL. The efficacy of the above regimens in our group of patients is comparable to that in clinical studies, even in patients with high-risk genetic features, such as 17p deletion and unmutated IgVH status. Treatment with venetoclax was also effective and well tolerated in patients after previous treatment with ibrutinib. The limitations of our evaluation are the small patient population and the short median follow-up of patients. In line with the conclusions of clinical trials and retrospective analysis from real-life practice, we can say that venetoclax-based treatment regimens are highly effective in patients with CLL in the first and higher line of treatment, with acceptable and well-manageable toxicity. This treatment is also effective in patients after previous treatment with ibrutinib.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"72 1-2","pages":"137-143"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and prognostic factors of PD-1 inhibitors combined with apatinib in advanced diffuse gastric cancer.","authors":"Beibei Chen, Huichen Zhao, Huihui Hu, Jinxi Huang, Yingjun Liu, Huifang Lv, Weifeng Xu, Jianzheng Wang, Caiyun Nie, Jing Zhao, Yunduan He, Saiqi Wang, Yuhang Wang, Xiaobing Chen","doi":"10.4149/neo_2025_241021N429","DOIUrl":"10.4149/neo_2025_241021N429","url":null,"abstract":"<p><p>Refractory diffuse gastric cancer (DGC) is rising in incidence and has a bad prognosis. Individuals who are administered second-line or subsequent therapies frequently exhibit diminished physical fitness, rendering them inappropriate for intensive treatment. Despite this, PD-1 inhibitors and anti-angiogenesis drug apatinib have demonstrated efficacy in advanced gastric cancer. This study aimed to evaluate the effectiveness, prognostic factors, and safety of PD-1 inhibitors in combination with apatinib in advanced DGC. The present study is a retrospective analysis of 34 patients with advanced DGC treated with apatinib combined with PD-1 inhibitors in the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2022. Apatinib 250 mg was administered to patients once a day. The median progression-free survival (mPFS) and the median overall survival (mOS) were estimated using Kaplan-Meier curves, whereas objective response rate (ORR), disease control rate (DCR), prognostic variables, and adverse events were among the other outcomes. Data from 34 patients were collected, and the ORR was 5.9% (2 out of 34), while the DCR was 55.9% (19 out of 34). The mPFS was 2.5 months (95% CI: 1.9-3.0), while the mOS was 6.8 months (95% CI: 3.7-9.9). Log-rank univariate analysis indicated that the mOS of patients with carcinoembryonic antigen (CEA) levels <4.7 ng/ml (11.3 months, 95% CI: 7.1-15.5) was significantly different from those with levels ≥4.7 ng/ml (2.7 months, 95% CI: 0.0-6.1) (p=0.008). A notable disparity in mOS and mPFS was observed between patients with CA125 <35 U/ml (7.7 months, 95% CI: 3.6-11.9) and those with CA125 ≥35 U/ml (2.5 months, 95% CI: 1.9-3.0) (p=0.003), as well as between patients with lactate dehydrogenase (LDH) <245 U/l (11.3 months, 95% CI: 7.2-15.5) and those with LDH ≥245 U/l (2.2 months, 95% CI: 1.5-2.9) (p=0.007), and between patients with PLTs <350×109/l (7.5 months, 95% CI: 6.4-8.7) compared to those with PLTs ≥350×109/l (1.7 months, 95% CI: 0.0-3.9) (p=0.001). Multivariate Cox regression analysis indicated that CA125, LDH, and PLT levels were independent prognostic variables. The occurrence of grade 3 or 4 treatment-related adverse events was 17.6% (6/34). The study suggests that the integration of PD-1 inhibitors and apatinib in second-line and subsequent therapies demonstrated promising efficacy and acceptable safety in advanced DGC patients. The concentrations of CA125, LDH, and PLTs may serve as prognostic indicators for DGC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"128-136"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative prognostic significance of primary cilia and cytoplasmic β-catenin expression in non-small cell lung cancer.","authors":"Blanka Rosova, Alzbeta Filipova, Dimitar Hadzi Nikolov, Marie Drösslerova, Radoslav Matej, Aneta Rozsypalova, Igor Richter, Bohuslav Melichar, Rostislav Mahel, Radka Stepanova, Radka Lohynska, Josef Dvorak","doi":"10.4149/neo_2024_241117N476","DOIUrl":"10.4149/neo_2024_241117N476","url":null,"abstract":"<p><p>The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.008). In the univariate Cox proportional hazard model, the hazard ratio was 1.653 in pts with present PC (p=0.026) and 1.851 in pts with higher cytoplasmic β-catenin (25-75%) (p=0.009). Multivariate testing of the whole group of 218 pts with NSCLC showed that the presence of PC was associated with a worse prognosis (p=0.018). In the subgroup of 125 pts with adenocarcinoma, OS was significantly improved in pts with higher membranous β-catenin expression (≥50%) than in pts with lower expression (<50%) (p=0.0300) and OS was significantly inferior in pts with higher cytoplasmic β-catenin expression (25-75%) than in pts with lower expression (<25%) (p=0.0004). Multivariate testing of the subgroup of pts with adenocarcinoma showed that cytoplasmic β-catenin (p<0.001) and pleural invasion (p=0.017) were associated with worse prognosis. The present results indicate a negative prognostic significance of PC and cytoplasmic β-catenin expression in NSCLC and a negative prognostic significance of cytoplasmic β-catenin expression in adenocarcinoma.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"594-602"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation status of selected genes in non-small cell lung carcinoma - current knowledge and future perspectives.","authors":"Adam Put, Katerina Smesny Trtkova, Jozef Skarda","doi":"10.4149/neo_2024_240925N403","DOIUrl":"10.4149/neo_2024_240925N403","url":null,"abstract":"<p><p>DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and the rare but highly aggressive large-cell neuroendocrine carcinoma (LCNEC). A comprehensive literature search was conducted in the PubMed database until August 17, 2024, using standardized keywords to identify reports on promoter methylation in NSCLC. Seventy-five studies were reviewed, focusing on the promoter methylation of key genes, such as APC, BRCA1, CDH1, CDH13, DAPK1, DLEC1, FHIT, GSTP1, hMLH1, MGMT, CDKN2A, RARβ, RASSF1, RUNX3, and TIMP3. These studies explored diagnostic, prognostic, epidemiological, and therapeutic aspects across NSCLC subtypes. Additionally, mutational profiles of TP53, RB1, KEAP1, and STK11 and expression patterns of ASCL1, DLL3, and NOTCH were analyzed. The findings suggest that LCNEC may serve as a biological bridge between non-small cell and small-cell lung carcinoma. Our analysis highlights that the methylation status of selected genes could enhance diagnosis, prognosis, and personalized treatment strategies in patients with NSCLC, particularly those with LCNEC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"511-532"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circ_0075829 regulates ferroptosis and immune escape in colon cancer cells through the miR-330-5p/TCF4 axis.","authors":"Huajun Fan, Yu Ding, Zhe Xiao, Shengbo Li, Yongbin Zheng","doi":"10.4149/neo_2024_240803N328","DOIUrl":"10.4149/neo_2024_240803N328","url":null,"abstract":"<p><p>Many lines of evidence suggest that circular RNAs (circRNAs) are closely associated with the occurrence and progression of colon cancer. The objective of this study was to investigate the regulatory effects and mechanisms of circ_0075829 on ferroptosis and immune escape in colon cancer. We utilized colon cancer cell lines and a xenograft mouse model to analyze the function of circ_0075829 in vitro and in vivo. The gene expression level was assessed by qRT-PCR and western blotting. Cell proliferation was evaluated using the CCK-8 assay. The targeting relationships between circ_0075829, miR-330-5p, and TCF4 were analyzed through a dual-luciferase reporter experiment and RNA pull-down experiment. Cytokine levels were measured using the ELISA assay. Fe2+, MDA, and SOD levels were tested using appropriate kits, and the ROS level was detected by immunofluorescence. Knockdown of circ_0075829 resulted in increased levels of Fe2+, ROS, and MDA and decreased levels of GPX4 and xCT proteins in cells. Furthermore, silencing of circ_0075829 increased the cell proliferation rates of CD8+T cells co-cultured with colon cells. Moreover, it also enhanced IFN-γ, IL-2, and TNF-α concentration in the supernatants of the co-culturing system and reduced PD-L1 protein expression levels. Subsequently, silencing of circ_0075829 induced ferroptosis and inhibited immune escape in vivo. Meaningfully, we certified that circ_0075829 functions as a sponge for miR-330-5p, leading to the upregulation of TCF4 expression. TCF4 was identified as a downstream target of miR-330-5p. Additionally, co-transfection with anti-miR-330-5p or TCF4 overexpression plasmid reversed the effects observed following the knockout of circ_0075829. Collectively, our research indicates that the circ_0075829 plays a significant role in regulating ferroptosis and immune escape in colon cancer by sponging miR-330-5p to modulate TCF4 expression.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"559-570"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}