Translational Oncology最新文献

{"title":"Transcriptomic profiling identifies a nucleotide metabolism-related signature with prognostic power in gliomas","authors":"","doi":"10.1016/j.tranon.2024.102068","DOIUrl":"10.1016/j.tranon.2024.102068","url":null,"abstract":"<div><h3>Objective</h3><p>Nucleotide metabolic reprogramming as a hallmark of cancer is closely related to the occurrence and progression of cancer. We aimed to comprehensively analyze the nucleotide metabolism-related gene set and clinical significance in gliomas.</p></div><div><h3>Methods</h3><p>The RNA sequencing data of 702 gliomas from the Cancer Genome Atlas (TCGA) dataset were included as the training set, and the RNA sequencing data from the other three datasets (CGGA, GSE16011, and Rembrandt) were used as independent validation sets. Survival curve, Cox regression analysis, time-dependent ROC curve and nomogram model were performed to evaluate prognostic power of signature. R language was the main tool for bioinformatic analysis and graphical work.</p></div><div><h3>Results</h3><p>Based on the expression profiles of nucleotide metabolism-related genes, consensus clustering identified two robust clusters with different prognosis. We then developed a nucleotide metabolism-related signature that was closely related to clinical, pathological, and genomic characteristics of gliomas. And ROC curve showed that our signature was a potential biomarker for mesenchymal subtype. Survival curve and Cox regression analysis revealed signature as an independent prognostic factor for gliomas. In addition, we constructed a nomogram model to predict individual survival. Finally, functional analysis showed that nucleotide metabolism not only affected cell division and cell cycle, but also was associated with immune response in gliomas.</p></div><div><h3>Conclusion</h3><p>We developed a nucleotide metabolism-related signature to predict prognosis and provided new insights into the role of nucleotide metabolism in gliomas.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324001955/pdfft?md5=a48aa05aa52aaad172e8a3e7adc97f83&pid=1-s2.0-S1936523324001955-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug tolerance and persistence in bacteria, fungi and cancer cells: Role of non-genetic heterogeneity","authors":"","doi":"10.1016/j.tranon.2024.102069","DOIUrl":"10.1016/j.tranon.2024.102069","url":null,"abstract":"<div><p>A common feature of bacterial, fungal and cancer cell populations upon treatment is the presence of tolerant and persistent cells able to survive, and sometimes grow, even in the presence of usually inhibitory or lethal drug concentrations, driven by non-genetic differences among individual cells in a population. Here we review and compare data obtained on drug survival in bacteria, fungi and cancer cells to unravel common characteristics and cellular pathways, and to point their singularities. This comparative work also allows to cross-fertilize ideas across fields. We particularly focus on the role of gene expression variability in the emergence of cell-cell non-genetic heterogeneity because it represents a possible common basic molecular process at the origin of most persistence phenomena and could be monitored and tuned to help improve therapeutic interventions.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324001967/pdfft?md5=b1a1cfdc34619c50cb162f0c676c4a74&pid=1-s2.0-S1936523324001967-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine withdrawal leads to the preferential activation of lipid metabolism in metastatic colorectal cancer","authors":"","doi":"10.1016/j.tranon.2024.102078","DOIUrl":"10.1016/j.tranon.2024.102078","url":null,"abstract":"<div><h3>Introduction</h3><p>Glutamine is a non-essential amino acid that is critical for cell growth. However, the differential metabolism of <span>l</span>-glutamine in metastatic versus primary colorectal cancer (CRC) has not been evaluated adequately.</p></div><div><h3>Materials and methods</h3><p>Differential expression of glutamine-related genes was determined in primary versus metastatic CRC. Univariate Cox regression and hierarchical clustering were used to generate a gene signature for prognostication. Untargeted metabolomics and ¹⁸O based fluxomics were used to identify differential metabolite levels and energy turnover in the paired primary (SW480) and metastatic (SW620) CRC cells. Western blot and qRT-PCR were used to validate differential gene expression. Subcellular localization of E-cadherin was determined by immunocytochemistry. Lipid droplets were visualized with Nile Red.</p></div><div><h3>Results</h3><p>The GO term “Glutamine metabolism” was significantly enriched in metastatic versus primary tumors. Supporting this, SW620 cells showed decreased membrane localization of E-cadherin and increased motility upon <span>l</span>-Glutamine withdrawal. A glutamine related signature associated with worse prognosis was identified and validated in multiple datasets. A fluxomics assay revealed a slower TCA cycle in SW480 and SW620 cells upon <span>l</span>-Glutamine withdrawal. SW620 cells, however, could maintain high ATP levels. Untargeted metabolomics indicated the preferential metabolism of fatty acids in SW620 but not SW480 cells. Lipids were mainly obtained from the environment rather than by <em>de novo</em> synthesis.</p></div><div><h3>Conclusions</h3><p>Metastatic CRC cells can display aberrant glutamine metabolism. We show for the first time that upon <span>l</span>-glutamine withdrawal, SW620 (but not SW480) cells were metabolically plastic and could metabolize lipids for survival and cellular motility.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002055/pdfft?md5=2fd3bbf6b172bb4b7bbf73f79c8dd045&pid=1-s2.0-S1936523324002055-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPIC-labeled CAFs: Key players in neoadjuvant chemotherapy resistance for gastric cancer","authors":"","doi":"10.1016/j.tranon.2024.102080","DOIUrl":"10.1016/j.tranon.2024.102080","url":null,"abstract":"<div><h3>Background</h3><p>Gastric cancer (GC) is the fourth leading cause of cancer deaths, with advanced cases having a median survival of less than one year. Neoadjuvant chemotherapy (NCT) is vital but faces drug resistance issues, partly due to cancer-associated fibroblasts (CAFs). Yet, specific CAF subpopulations contributing to resistance are poorly understood.</p></div><div><h3>Methods</h3><p>Differentially expressed genes (DEGs) between chemosensitive and resistant GC patients were identified using GEO2R. Single-cell sequencing (scRNA-seq) identified CAF-related genes. Immunohistochemistry verified key genes in NCT-treated GC samples, analyzing their correlation with tumor regression grade (TRG) and clinicopathological characteristics.</p></div><div><h3>Results</h3><p><em>PPIC</em> as a gene highly expressed in CAFs was closely associated with NCT resistance in gastric cancer. Immunohistochemistry results revealed positivity for the expression of cyclophilin C (CypC), encoded by <em>PPIC</em>, in the 5-fluorouracil and cisplatin NCT resistant and -sensitive groups of gastric cancer patients at rates of 69.7 % (76/109) and 43.6 % (24/55), respectively (<em>p</em> &lt; 0.001). The high expression of CypC in CAFs was positively correlated to tumor size (<em>p</em> = 0.025), T stage (<em>p</em> = 0.004), TNM stage (<em>p</em> = 0.004), and vascular invasion (<em>p</em> = 0.027). In cancer cells the expression of CypC was associated with OS (<em>p</em> = 0.026). However, in CAFs, CypC expression was not related to OS (<em>p</em> = 0.671).</p></div><div><h3>Conclusions</h3><p><em>PPIC</em>-labeled CAF subgroups are related to NCT resistance and poor prognosis in GC and they may cause drug resistance through signaling pathways such as glucose metabolism and extracellular matrix remodeling. However, the exact mechanism behind the involvement of <em>PPIC</em>-labeled CAF in drug resistance of GC requires further study.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002079/pdfft?md5=92c45df01dec332f5d2062b8f4061b76&pid=1-s2.0-S1936523324002079-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytochrome P450 F3 promotes colorectal cancer via inhibiting NRF2-mediated ferroptosis","authors":"","doi":"10.1016/j.tranon.2024.102077","DOIUrl":"10.1016/j.tranon.2024.102077","url":null,"abstract":"<div><p>Cytochrome P450 F3 (CYP4F3) is recognized as a disease-associated immune response initiator that is involved in the synthesis of cholesterol, steroids, and lipids. This study identified the upregulation of <em>CYP4F3</em> expression in colorectal cancer (CRC) and its association with poor patient prognosis through a comparative analysis between CRC tumor tissues with normal tissues from public databases. The overexpression of <em>CYP4F3</em> in CT26.wt and SW620, promoted cell proliferation and migration, a reduction of cellular oxidative stress, an up-regulation of the oxidative stress-related pathway NRF2, and an inhibition of cellular ferroptosis. Additionally, inhibition of NRF2 activity stimulated cellular ferroptosis when <em>CYP4F3</em> was overexpressed. Ferroptosis, characterized by iron-dependent lipid peroxidation, is a non-apoptotic way of cell death with a critical role in cancer development. When given a ferroptosis agonist to CYP4F3-overexpression CRC cells, NRF2 was activated, and cell proliferation and migration were reduced. Furthermore, the mice subcutaneously injected with CYP4F3-overexpression CT26.wt cells formed significantly larger tumors compared to the CYP4F3-vector CT26.wt cell group. This study systematically identified an important role of <em>CYP4F3</em> in CRC development as a regulator of CRC cells to escape ferroptosis via NRF2, highlighting the significance of <em>CYP4F3</em> as a potential therapeutic target for CRC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002043/pdfft?md5=a81035f8302fc592c88b9a1bf0c19f0b&pid=1-s2.0-S1936523324002043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8+ T cells","authors":"","doi":"10.1016/j.tranon.2024.102074","DOIUrl":"10.1016/j.tranon.2024.102074","url":null,"abstract":"<div><p>Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8⁺ <em>T</em> cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8⁺ <em>T</em> cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8⁺ <em>T</em> cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8⁺ <em>T</em> cells was lower in EGFR-mutated NSCLC. In addition, CD8⁺ <em>T</em> cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8⁺ <em>T</em> cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8⁺ <em>T</em> cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8⁺T cells in mice.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002018/pdfft?md5=d8366bc3c0ddded909e91a182cfd23df&pid=1-s2.0-S1936523324002018-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of CXCL10 and MIP-3a reveals their potential clinical application in hepatocellular carcinoma","authors":"","doi":"10.1016/j.tranon.2024.102071","DOIUrl":"10.1016/j.tranon.2024.102071","url":null,"abstract":"<div><p>Chemokines play a crucial role in the pathogenesis of patients with hepatocellular carcinoma (HCC). The expression levels of interferon-γ-induced protein-10 (CXCL10) and macrophage inflammatory protein-3α (MIP-3a) were investigated to clarify their clinical significance in HCC.</p><p>The protein levels of CXCL10 and MIP-3a in the serum of 105 HBV-associated HCC patients, 50 patients with liver cirrhosis (LC), 50 patients with chronic hepatitis B (CHB) and 50 healthy donors (HC) were detected by liquid chip technology (Luminex) or ELISA. In addition, their mRNA levels were also determined in liver cancer and adjacent cancer tissue (paracancer; ParaCa) from 65 HCC patients. The online database UALCAN was used to analyze the association between CXCL10 and pathological manifestations of liver cancer. In addition, the diagnostic value of CXCL10/MIP-3a and AFP in HCC patients was determined by analyzing the Receiver Operating Characteristic Curve (ROC).</p><p>The protein concentrations of CXCL10 and MIP-3a were significantly higher in the HCC group than in the LC, CHB and HC groups. CXCL10 in sera and liver cancer tissues is significantly positively correlated with ALT, but no significance between CXCL10 in ParaCa tissues and sera-ALT. Their mRNA is significantly higher in cancer tissues than in ParaCa tissues. The areas under the ROC curve of CXCL10, MIP-3a, CXCL10 and MIP-3a combined and AFP were 0.9169, 0.9261, 0.9299 and 0.7880, respectively. Elevated chemokines CXCL10 and MIP-3a in HCC patients may be associated with the clinical manifestation of HCC and could be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324001980/pdfft?md5=7c7e47e1f9ae9f496f30cbb441a10968&pid=1-s2.0-S1936523324001980-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SNCA in the treatment of malignant ascites in gastrointestinal cancer","authors":"","doi":"10.1016/j.tranon.2024.102075","DOIUrl":"10.1016/j.tranon.2024.102075","url":null,"abstract":"<div><p>Peritoneal tumor dissemination and subsequent malignant tumor ascites (MTA) occur unexpectedly and repeatedly in patients with gastrointestinal (GI) cancers, and worsen quality of life and prognosis of the patients. Various treatments have been clinically developed for these patients, while most of the MTA cases are refractory to the treatments. Thus, effective treatments are urgently needed to improve the clinical outcomes. In this study, we identified α-synuclein (SNCA) as an immunological determinant of MTA progression in GI cancer through translational research using mouse tumor models and clinical specimens collected from gastric cancer patients. We found that the SNCA⁺ subsets were significantly increased in CD3⁺ T cells, CD56⁺ NK cells, and CD11b⁺ myeloid cells within MTA and peripheral blood cells (PBCs) of MTA cases, albeit almost absent in PBCs of healthy donors, and spleen of naive mice. Of note, the SNCA⁺ T-cell subset was rarely seen in patients that intraperitoneal lavage fluid without tumor cells was collected before surgery as a tumor-free control, suggesting a possible cancer-induced product, especially within the peritoneal cavity. In vivo treatment with anti-SNCA blocking mAb significantly induced anti-tumor effects in mouse MTA models, and synergistically improved anti-PD1 therapeutic efficacy, providing a significantly better prognosis. These suggest that SNCA is involved in severe immunosuppression in the MTA cases, and that blocking SNCA is effective in dramatically improving the immune status in the hosts. Targeting SNCA will be a promising strategy to improve clinical outcomes in the treatment of GI cancer patients, especially with MTA.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193652332400202X/pdfft?md5=5bd38bce1831a8da1a5d032201f80726&pid=1-s2.0-S193652332400202X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SnoRNA U50A mediates everolimus resistance in breast cancer through mTOR downregulation","authors":"","doi":"10.1016/j.tranon.2024.102062","DOIUrl":"10.1016/j.tranon.2024.102062","url":null,"abstract":"<div><p>Breast cancer remains the most prevalent cancer in women globally, posing significant challenges in treatment due to the inevitable development of resistance to targeted therapies like everolimus, an mTOR inhibitor. While several mechanisms of resistance have been proposed, the role of snoRNAs in this context remains inadequately explored. Our study unveils a novel connection between snoRNAs and everolimus resistance, focusing on the snoRNA U50A. We discovered that U50A negatively regulates mTOR signaling by transcriptionally downregulating mTOR gene expression, which consequently leads to decreased sensitivity to everolimus treatment. Through RNA sequencing, gene set enrichment analyses, and experimental validations, we established that U50A overexpression in breast cancer cells results in mTOR downregulation and subsequently, everolimus desensitization. Clinical results further supported our findings, showing a higher prevalence of everolimus resistance in tumors with elevated U50A expression. Moreover, our results suggest that U50A's effect on mTOR is mediated through the suppression of the transcription factors c-Myc, with a notable impact on cancer cell viability under everolimus treatment. This study not only highlights the complex role of snoRNAs in cancer drug resistance but also proposes U50A as a potential biomarker for predicting everolimus efficacy in breast cancer treatment.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193652332400189X/pdfft?md5=70c271e0d724276441896931a1794094&pid=1-s2.0-S193652332400189X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-34b promotes oxidative stress and induces cellular senescence through TWIST1 in human cervical cancer","authors":"","doi":"10.1016/j.tranon.2024.102063","DOIUrl":"10.1016/j.tranon.2024.102063","url":null,"abstract":"<div><h3>Purpose</h3><p>The aim of this research was to elucidate the role of miR-34b in cervical cancer progression and the underlying mechanism behind the miR-34b-mediated tumor suppression. The study revealed the role of miR-34b as a senescence inducer and serves as a potential therapeutic target in developing combination therapy with senotherapeutics.</p></div><div><h3>Methods</h3><p>MiR-34b was ectopically expressed in cervical cancer cell lines using a tetracycline inducible system and its effects on cell viability, apoptosis, senescence, DNA damage and oxidative stress were studied using MTT assay, acridine orange/ ethidium bromide staining, senescence associated β-galactosidase assay, gamma H2AX foci staining assay, western blotting and specific dyes for the detection of total and individual ROS species.</p></div><div><h3>Results</h3><p>Ectopic expression of miR-34b promoted cellular senescence but no significant induction of apoptosis was observed in cervical cancer cell lines. MiR-34b promoted increase in oxidative stress through increase in total and individual ROS species and contributed to increase in cellular senescence. Mechanistically, miR-34b mediates its action by targeting TWIST1 as evidenced by the similar actions of TWIST1 shRNA in cervical cancer cell lines. Furthermore, our study revealed TWIST1 is one of the most significant targets of miR-34b targetome and identified RITA as a novel senolytic agent for use in combination therapy with miR-34b.</p></div><div><h3>Conclusion</h3><p>MiR-34b promotes cellular senescence and oxidative stress by targeting TWIST1, a known oncogene and EMT regulator. This study delved into the mechanism of miR-34b-mediated tumor suppression and provided novel insights for development of miR-34b based therapeutics for cervical cancer.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324001906/pdfft?md5=b1e31bf9c18765bcb4a57870cdb15d86&pid=1-s2.0-S1936523324001906-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}