Journal of Cancer最新文献

{"title":"Causal associations of BAFF-R on IgD+ CD24- B cell immune cell trait with hepatocellular carcinoma and the mediating role of phenylacetylglutamate levels: a Mendelian randomization study.","authors":"Xuan Zhu, Zongchao Qiu, Maochun Yang, Jiali Yang, Lingxi Kong, Limin Li, Yingting Huang, Li Xie","doi":"10.7150/jca.96059","DOIUrl":"10.7150/jca.96059","url":null,"abstract":"<p><p>We conducted a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between immune cell traits and hepatocellular carcinoma (HCC) and identified the mediating factor of metabolites. The exposure factors were immune cell traits, the mediators were metabolites, and the outcome variable was HCC. Inverse-variance weighted method (IVW) was the main method. Weighted median, MR-Egger regression, weighted mode, simple mode, and MR pleiotropy residual sum and outlier (MRPRESSO) methods were used as complementary methods. The results were tested by using the Bayesian weighted Mendelian randomization (BWMR) approach in our MR study. Subsequently, the potential mediating effect was investigated by conducting a two-step mediation analysis. We identified 26 traits with suggestive correlations between immune cell traits and HCC, with 4 immune cell traits among them having causal correlations with HCC. There were no causal correlations between HCC and immune cell traits in the reverse MR analysis. In the mediation analysis, we found a positive causal association between B cell-activating factor receptors (BAFF-R) on IgD+ CD24- B cell and HCC [IVW: odd ratio (OR), 0.845; 95% CI, 0.759-0.942; p = 0.002]. Phenylacetylglutamate (PAG) levels mediated 7.353% of the causal pathway from BAFF-R on IgD+ CD24- B cell and HCC. In conclusion, BAFF-R on IgD+ CD24- B cell lowers risk of HCC, with PAG levels playing a mediating role.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGR1 Promotes Erastin-induced Ferroptosis Through Activating Nrf2-HMOX1 Signaling Pathway in Breast Cancer Cells.","authors":"Zhirong Lin, Zifei Liu, Zhilong Pan, Yunyi Zhang, Xinyu Yang, Yaxin Feng, Ruihua Zhang, Wenfeng Zeng, Chang Gong, Jianing Chen","doi":"10.7150/jca.95328","DOIUrl":"10.7150/jca.95328","url":null,"abstract":"<p><p><b>Purpose:</b> Early growth response 1 (EGR1) is a crucial transcription factor composed of zinc finger structures, inhibitory and activating regulatory regions. We identified the biological effect and molecular mechanisms of EGR1 in breast cancer (BC). <b>Methods:</b> We used qRT-PCR, western blot and immunohistochemistry to examine the expression of EGR1 in BC samples. CCK-8 and colony assay were performed to reveal the effect of EGR1 on the proliferation of BC cells. LDH release assay, MCB assay, MDA assay, C-AM assay and TMRE assay were performed to measure the levels of LDH release, GSH, MDA, LIP and mitochondrial membrane potential. The regulation of EGR1 on the expression of Nrf2 and HMOX1 was investigated through Western blot. Xenograft models were conducted to determine the impact of EGR1 overexpression on BC <i>in vivo</i>. <b>Results:</b> The expression of EGR1 was downregulated in BC tissues compared with the normal tissues, and lower expression of EGR1 associated with poorer clinical outcome in BC patients. Through <i>in vitro</i> experiments, we found that EGR1 downregulation facilitated the proliferation of BC cells, and overexpression of EGR1 inhibited the proliferation of BC cells. In addition, EGR1 knockdown alleviated erastin-induced ferroptosis and overexpression of EGR1 facilitated erastin-induced ferroptosis in BC cells. Moreover, overexpression of EGR1 facilitated the anti-tumor effect caused by erastin <i>in vivo</i>. Mechanistically, the phosphorylation levels of Nrf2 and the expression of HMOX1 were reduced due to the downregulation of EGR1, and increased due to the upregulation of EGR1. Additionally, the finding that EGR1 facilitated erastin-induced ferroptosis was alleviated by the inhibition of Nrf2-HMOX1. <b>Conclusion:</b> The expression of EGR1 is downregulated in BC, which is correlated with poor prognosis of BC patients. EGR1 suppresses the proliferation of BC cells and facilitates erastin-induced ferroptosis by activating Nrf2-HMOX1 signaling pathway in BC cells.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUB1 Promotes Glioblastoma Growth by Inhibiting the JAK2/STAT1 Signaling Pathway.","authors":"Jun Yang, Na Zhang, Zesong He, Junyi Xiong, Wei Meng, Chengcheng Xue, Li Ying, Meihua Li, Mei Liu, Taohui Ouyang","doi":"10.7150/jca.96360","DOIUrl":"10.7150/jca.96360","url":null,"abstract":"<p><p><b>Background:</b> OTUB1, an essential deubiquitinating enzyme, is upregulated in various types of cancer. Previous studies have shown that OTUB1 may be an oncogene in glioblastoma multiforme (GBM), but its specific regulatory mechanism remains unclear. This study aimed to investigate the mechanism by which OTUB1 and the JAK2/STAT1 signaling pathway co-regulate the growth of GBM. <b>Methods:</b> Using bioinformatics, GBM tissues, and cells, we evaluated the expression and clinical significance of OTUB1 in GBM. Subsequently, we explored the regulatory mechanisms of OTUB1 on malignant behaviors in GBM <i>in vitro</i> and <i>in vivo</i>. In addition, we added the JAK2 inhibitor AZD1480 to explore the regulation of OTUB1 for JAK2/STAT1 pathway in GBM. <b>Results:</b> We found that OTUB1 expression was upregulated in GBM. Silencing OTUB1 promotes apoptosis and cell cycle arrest at G1 phase, inhibiting cell proliferation. Moreover, OTUB1 knockdown effectively inhibited the invasion and migration of GBM cells, and the opposite phenomenon occurred with overexpression. <i>In vivo</i> experiments revealed that OTUB1 knockdown inhibited tumor growth, further emphasizing its crucial role in GBM progression. Mechanistically, we found that OTUB1 was negatively correlated with the JAK2/STAT1 pathway in GBM. The addition of the JAK2 inhibitor AZD1480 significantly reversed the effects of silencing OTUB1 on GBM. <b>Conclusion:</b> Our study reveals a novel mechanism by which OTUB1 inhibits the JAK2/STAT1 signaling pathway. This contributes to a better understanding of OTUB1's role in GBM and provides a potential avenue for targeted therapeutic intervention.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MPP7 mediates EMT via Wnt/β-catenin pathway to promote polarity changes in epithelial ovarian cancer cells.","authors":"Chunlin Tao, Xiaoge Ni","doi":"10.7150/jca.96185","DOIUrl":"10.7150/jca.96185","url":null,"abstract":"<p><p>Ovarian cancer is one of the gynecological malignancies with the highest mortality rate. Its widespread metastasis is difficult to cure, and the beneficiaries of targeted therapy are still limited, which has been a long-standing bottleneck problem. MAGUK P55 scaffold protein 7 (MPP7) plays an important role in the establishment of epithelial cell polarity, but its potential significance in epithelial ovarian cancer is still unclear. In this study, we investigated the expression profile of MPP7 and its functional role in epithelial ovarian cancer. Through analysis of TCGA and GEO databases, combined with immunohistochemical staining of ovarian tumor tissue chips, it was found that MPP7 is significantly overexpressed in epithelial ovarian cancer tissue, and its high expression is closely related to poor prognosis of patients. It has been verified through cell function experiments that interference with MPP7 can inhibit the proliferation, migration, and invasion of ovarian cancer cells <i>in vitro</i>. Performing planar polarity immunofluorescence staining on ovarian cancer cells revealed that interference with MPP7 can cause polarity changes in ovarian cancer cells. The transcriptome sequencing results of the ovarian cancer database were analyzed, and Western Blot was used to verify that MPP7 may mediate EMT via Wnt/β-catenin signaling pathway and promote changes in cell polarity in human epithelial ovarian cancer, thereby promoting cancer progression, demonstrating the potential of MPP7 as a new biomarker and target for the diagnosis and treatment of ovarian cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Hypoxia and Mitochondrial-related Gene Signature and Prediction of Prognostic Model in Lung Adenocarcinoma.","authors":"Wenhao Zhao, Hua Huang, Zexia Zhao, Chen Ding, Chaoyi Jia, Yingjie Wang, Guannan Wang, Yongwen Li, Hongyu Liu, Jun Chen","doi":"10.7150/jca.97374","DOIUrl":"10.7150/jca.97374","url":null,"abstract":"<p><p><b>Background:</b> The correlation between hypoxia and tumor development is widely acknowledged. Meanwhile, the foremost organelle affected by hypoxia is mitochondria. This study aims to determine whether they possess prognostic characteristics in lung adenocarcinoma (LUAD). For this purpose, a bioinformatics analysis was conducted to assess hypoxia and mitochondrial scores related genes, resulting in the successful establishment of a prognostic model. <b>Methods:</b> Using the single sample Gene Set Enrichment Analysis algorithm, the hypoxia and mitochondrial scores were computed. Differential expression analysis and weighted correlation network analysis were employed to identify genes associated with hypoxia and mitochondrial scores. Prognosis-related genes were obtained through univariate Cox regression, followed by the establishment of a prognostic model using least absolute shrinkage and selection operator Cox regression. Two independent validation datasets were utilized to verify the accuracy of the prognostic model using receiver operating characteristic and calibration curves. Additionally, a nomogram was employed to illustrate the clinical significance of this study. <b>Results:</b> 318 differentially expressed genes associated with hypoxia and mitochondrial scores were identified for the construction of a prognostic model. The prognostic model based on 16 genes, including PKM, S100A16, RRAS, TUBA4A, PKP3, KCTD12, LPGAT1, ITPRID2, MZT2A, LIFR, PTPRM, LATS2, PDIK1L, GORAB, PCDH7, and CPED1, demonstrates good predictive accuracy for LUAD prognosis. Furthermore, tumor microenvironments analysis and drug sensitivity analysis indicate an association between risk scores and certain immune cells, and a higher risk scores suggesting improved chemotherapy efficacy. <b>Conclusion:</b> The research established a prognostic model consisting of 16 genes, and a nomogram was developed to accurately predict the prognosis of LUAD patients. These findings may contribute to guiding clinical decision-making and treatment selection for patients with LUAD, ultimately leading to improved treatment outcomes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administering immunotherapy after anti-vascular targeted therapy improves overall survival of patients with metastatic clear cell renal cell carcinoma.","authors":"Zhiwei Hou, Long Lai, HuaGuo Wu, Benkui Zou, Ni Xu, Dongyuan Zhu, Xiaokun Wang, Hui Zhang","doi":"10.7150/jca.96514","DOIUrl":"10.7150/jca.96514","url":null,"abstract":"<p><strong>Background: </strong>The Food and Drug Administration of the United States has approved several drugs for treating advanced metastatic renal cell carcinoma, including anti-vascular tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Options for first-line therapy include monotherapy or combination therapy. However, selecting a suitable first-line and second-line treatments to improve overall survival remains an unresolved issue.</p><p><strong>Objective: </strong>To evaluate the overall survival (OS) and progression-free survival (PFS) of patients with metastatic clear cell renal cell carcinoma (mRCC). Patients were divided into several grouped according to the treatment sequence of TKI and anti PD-1 administration. The overall survival benefit was evaluated based on the order of administration of anti PD-1 and TKI.</p><p><strong>Patients and methods: </strong>In this retrospective propensity-matched cohort study, we identified 135 patients with mRCC treated at the Affiliated Cancer Hospital of Shandong First Medical University from January 1, 2017, to December 31, 2022. These patients had received anti PD-1 treatment as part of their first or second line of therapy. Statistical analysis was performed from June 1, 2023, to August 1, 2023. The primary outcome measure was OS, from the date of diagnosis to death or the last follow-up. PFS was monitored during treatment. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. By comparing the complete treatment course of patients, the survival of patients in different groups was compared according to the number of immunotherapy lines.</p><p><strong>Results: </strong>The final cohort comprised 135 patients, of whom 84 received first-line therapy with anti PD-1 (include 6 patients treated with anti PD-1 (tislelizumab, carrelizumab, toripalimab or sintilizumab) alone and 78 patients treated with anti PD-1 combined with anti-vascular TKI (axitinib, sunitinib, solfanitinib or pazopanib)). The remaining 51 patients were treated with anti PD-1 as second-line therapy following an initial regime of TKIs. Patients were initially categorized based on whether anti PD-1 were used in the first-line treatment. It was observed that the OS of patients receiving first-line targeted therapy was higher than those receiving first-line immunotherapy, with a median OS of 33 months versus 15 months. To investigate this outcome further, we refined the patient groups based on the administration sequence of anti PD-1 and TKIs in the treatment regimen. We found that the median PFS of patients with first-line treatments of TKI combined with anti PD-1 was 3.5 months, compared to 14.5 months when TKI combined with anti PD-1 followed first-line TKI (<i>p</i>=0.0092). The median PFS for second-line treatments was 6.5 months versus 15 months (<i>p</i>=0.0014). Similarly, the median OS was 16.66 months and 31.88 months, respectively (<i>p</i>=0.008).</p><p","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between sex differences in drinking, smoking, and exercising and the incidence of malignancies and medical procedures: a cross-sectional study of 21,916 participants in China.","authors":"Mingyan Hao, Yifan Li, Wenjun Ma, Lizheng Wang, Janzhong Zheng, Yibo Wu","doi":"10.7150/jca.95456","DOIUrl":"10.7150/jca.95456","url":null,"abstract":"<p><p><b>Objectives:</b> The unresolved issue of the relationship between sex differences in tea, coffee, and beverage consumption and malignancy risk prompted our study in 2022. <b>Methods:</b> Logistic proportional hazards models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in our investigation of the associations between cancer risk and tea, coffee, and beverage consumption. <b>Results:</b> Our findings revealed that frequent consumption of white tea significantly reduced the occurrence of malignant tumours, but this effect was detected only in the fully adjusted model for males (OR: 0.736, 95% CI: 0.095-5.704). The amount of sugar added to coffee was associated with an increased risk of malignancy in a dose-dependent manner (P for trend = 0.001), with significance observed for both men (P for trend = 0.049) and women (P for trend = 0.005) in the final model. Notably, individuals who consumed more than 2100 ml of sugary beverages daily had a statistically significant reduction in malignancy risk (OR: 0.219, 95% CI: 0.052-0.917). Interestingly, the intake of sugary beverages had a protective effect on cancer incidence, with a significant effect on males (P for trend = 0.031) but not females (P for trend = 0.096) in the final model. <b>Conclusions:</b> Our study highlights the substantial impact of regular white tea consumption on reducing the risk of malignant tumours in males. This study first reported that the potential protective effect of consuming sugary beverages is predominantly observed in males, and a correlation between the amount of sugar added to coffee and a heightened risk of malignancy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Anti-Tumor Efficacy Achieved by Reversing Drug Resistance through the Regulation of the Tumor Immune Microenvironment with IL-12 and Osimertinib Combination Therapy.","authors":"Huiqin Ding, Lijuan Wu, Huan Qin, Wenhui Fu, Yajun Wang, Mingyuan Wu, Jiangang Wang, Yantao Han","doi":"10.7150/jca.95407","DOIUrl":"10.7150/jca.95407","url":null,"abstract":"<p><p>The objective of this study was to investigate the role of IL-12 in enhancing the anti-tumor efficacy of the small molecule targeted drug osimertinib in resistant tumor models and reversing resistance mechanisms. We utilized paired non-small cell lung cancer H1975 tumor tissues, establishing mouse tumor models with diverse tumor immune microenvironments. Analytical methods including immunohistochemistry and immunofluorescence were employed to compare immune cell infiltration, cytokines, effector molecules, and protein changes in resistant signaling pathways in tumor tissues, shedding light on IL-12's mechanism of action in enhancing osimertinib efficacy and reversing resistance. Results showed that osimertinib monotherapy had limited tumor suppression, whereas IL-12 exhibited more significant anti-tumor effects. Combination therapy groups demonstrated even greater tumor suppression with increased immune cell infiltration, elevated immune-related factor secretion, reduced immunosuppressive MDSCs, and decreased resistance-related signaling pathway markers. In conclusion, IL-12 enhances anti-tumor efficacy and reverses osimertinib resistance through various mechanisms, including increased immune cell infiltration, reduced immunosuppressive MDSCs, enhanced immune cell granzyme and IFN-γ release, decreased PDL-1 expression, improved tumor microenvironment, restored immune surveillance, and heightened cancer cell sensitivity to osimertinib.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Pulmonary microbiota on lung cancer treatment-related pneumonia.","authors":"Maoyuan Zhao, Wang Hou, Dan Pu, Zhixi Li, Li Tu, Calista Jia Ling Ow, Jie Tian, Weimin Li","doi":"10.7150/jca.93818","DOIUrl":"10.7150/jca.93818","url":null,"abstract":"<p><p><b>Background:</b> The use of immunotherapy is progressively expanding for the treatment of lung cancer, either alone or in combination with radiotherapy. However, treatment-related adverse events, especially pneumonia, significantly limit the drug's effectiveness in treating lung cancer. The occurrence of lung cancer, immunotherapy, and pulmonary radiotherapy can all contribute to the imbalance in the pulmonary microbiota, rendering the lungs more susceptible to inflammatory reactions. <b>Methods:</b> Mouse models of lung transplantation tumor were treated with either PD-1 monoclonal antibody or radiotherapy alone, or in combination. The differences in lung inflammation among the different treatment groups were regularly observed by micro-CT. Further, bronchoalveolar lavage fluid was extracted for macrogenomic and cytokine detection. The transcriptional genome of tumor-filled lung tissue was also sequenced. <b>Results:</b> When treated with a combination of PD-1 and radiotherapy, the CT scans showed more severe pulmonary inflammation. However, with the addition of continuously administered antibiotics, no exacerbation of pneumonia signs was observed. Moreover, the differential gene expression and cytokine profiles in the combination treatment group differed from those in the PD-1 monotherapy group and the radiotherapy monotherapy group. This discrepancy does not seem to be a straightforward superimposition of radiation-induced pneumonia and immune-related pneumonia. Further exploration of changes in pulmonary microbiota revealed specific bacterial interactions with DEGs and cytokines. <b>Conclusions:</b> The underlying causes of this susceptibility are intricate and may be associated with the complexity of pulmonary microbiota imbalance, along with fluctuations in the abundance of specific microbiota species.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miRNA-146a-5p Derived from Senescent Hepatocellular Carcinoma Cells Promotes Aging and Inhibits Aerobic Glycolysis in Liver Cells via Targeting IRF7.","authors":"Sijia Yang, Ang Li, Lihong Lv, Zhihua Zheng, Peiqing Liu, Jun Min, Jinxing Wei","doi":"10.7150/jca.96500","DOIUrl":"10.7150/jca.96500","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a major global health challenge. Chemotherapy can cause HCC cells to become senescent. Senescent HCC cells play an important role in inhibiting or promoting cancer by producing extracellular vesicles with a senescence-associated secretory phenotype (EV-SASP). miRNA can be strongly upregulated in EV-SASP during the aging process and can substantially alter the phenotypic characteristics of cells. MiRNA microarray analysis revealed that miRNA-146a-5p was highly expressed in oxaliplatin- and H₂O₂-induced senescent Huh7 cells, and RT‒PCR confirmed its significant upregulation in exosomes. The transcriptome sequencing results of Huh7 cells overexpressing miRNA-146a-5p suggested that miRNA-146a-5p could regulate HCC cell glycolysis. Subsequently, a dual luciferase assay was used to verify whether miRNA-146a-5p can interact with IRF7 to promote aging. The key functions of miRNA-146a-5p and IRF7 in aerobic glycolysis in liver cancer cells were determined through experiments analyzing glucose uptake, lactate production, the oxygen consumption rate (OCR) and the proton efflux rate (PER). Subsequently, the regulatory effect of IRF7 on the key glycolytic gene PFKL was confirmed through luciferase reporter assays. The western blot experiment results showed that miR-146a-5p can activate CHK2 and p53 phosphorylated proteins by targeting IRF7, and upregulate p21 protein. Overexpression of miRNA-146a-5p effectively inhibited the aerobic glycolytic function of HCC cells. Moreover, silencing IRF7 effectively inhibited aerobic glycolysis. MiR-146a-5p. MiR-146a-5p can activate the phosphorylation of CHK2 phosphorylation protein and its downstream protein p53 by targeting IRF7, and the activated p53 upregulates the expression of p21. Our study revealed that exosomal miRNA-146a-5p produced by aging HCC cells, can inhibit HCC cell proliferation through inhibiting aerobic glycolysis and promote HCC cell aging by activating CHK2/p53/p21 signaling way by targeting IRF7.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}