Frontiers in Oncology
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2025
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IF 3.3
Yue-Ying Li,Hui Liu,Jia-Lu Feng,Wen-Yan Tian,Juan Du,Li-Ping Zhang
Introduction Endometrial cancer (EC) is a growing global health concern. Understanding the molecular mechanisms driving EC is crucial for developing effective diagnostic and therapeutic strategies. This study investigates the roles of DLL3 and miR-508-5p in EC progression and explores a therapeutic approach using engineered exosomes to modulate their expression. Methods TCGA data were analyzed, in vitro and in vivo experiments were performed to assess DLL3 and miR-508-5p function, and bioinformatics was used to confirm their interaction. Mesenchymal stem cells (MSCs) were engineered to produce miR-508-5p-overexpressing exosomes, and their therapeutic effects were tested in mouse models. Results Elevated DLL3 and downregulated miR-508-5p were observed in EC and correlated with poor outcomes. miR-508-5p directly targets DLL3. Engineered exosomes restored miR-508-5p, inhibited DLL3, and reduced tumor growth and metastasis in mouse models. Discussion The findings highlight the roles of DLL3 and miR-508-5p in EC. Targeting the miR-508-5p/DLL3 axis via exosome-mediated delivery represents a promising therapeutic strategy for EC.
研究领域:
分子生物学
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肿瘤学
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基因治疗
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-26
·
IF 6
Wei Xuehua,Xiong Xiangpeng,Wang Pingping,Zhang Shufang,Peng Dongxian
Background The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance.Methods High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues.Results High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein–protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC.Conclusion This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
GYNECOLOGIC ONCOLOGY
·
2025
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IF 4.1
Hanfei Xie,Lu Sun,Shili Yao,Xuefei Tian,Liming Jin,Yujie Dai,Yuanzheng Li,Yuxuan Li,Jianmin Fang,Peng Guo,Yingli Zhang
Objective The incidence of mortality and morbidity from endometrial cancer (EC) is increasing annually, and there is a paucity of effective targeted therapies for the condition. Antibody-drug conjugates (ADCs) represent a promising approach to tumor-targeted therapy. In this study, we aim to identify a novel molecular target for the preclinical development of EC-targeted ADCs. Methods Through quantitative and unbiased bioinformatics analyses intercellular adhesion molecule-1 (ICAM1) was identified as a potential cell membrane target. Two ADCs, ICAM1-MMAE and ICAM1-DXd, were subsequently developed by conjugating ICAM1 monoclonal antibodies with microtubule inhibitors and DNA topoisomerase inhibitors, respectively. The preclinical efficacy and biosafety of these ICAM1 ADCs were validated in both in vitro and in vivo models. Furthermore, transcriptomic analysis was conducted to elucidate the therapeutic effects of the ICAM1 ADCs. Results Quantitative flow screening and bioinformatics analyses revealed significant overexpression of ICAM1 in EC. ICAM1-MMAE and ICAM1-DXd were developed using clinically effective linkers and payloads. In preclinical models, ICAM1 ADCs showed superior antitumor efficacy compared to standard chemotherapy, achieving sustained tumor regression with an excellent safety profile in both subcutaneous and orthotopic xenograft models. Transcriptomic analysis further revealed that ICAM1-DXd potently activated tumor immunity. Conclusions ICAM1 was identified as a promising cell membrane protein target for ADC development in EC. As-synthesized ICAM1 ADCs demonstrated potent antitumor activity, favorable biosafety profiles in vitro and in vivo , and the ability to activate tumor immunity. These findings support the potential of ICAM1 ADCs as a therapeutic strategy and warrant further investigation in clinical studies.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2024
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IF 3.1
Chen Hua,Han Cailing,Ha Chunfang
Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecologic tumors. Due to the high recurrence and metastasis of UCEC, it is crucial for patients to find new biomarkers for diagnosis and therapy. In this study, R software and the TCGA database were used to screen candidate UCEC predictive markers. Western blot and RT-qPCR were performed to detect protein and mRNA expression of EXT1 in UCEC cell lines. In addition, MTT assay, flow cytometry, transwell assay, and wound healing assay were conducted to assess the cell viability, apoptosis, invasion, and migration in UCEC cells. Overlap-extension PCR technique was employed to construct the vector targeting the deletion of the methylated segment of EXT1. The results showed that a total of 11 candidate genes were obtained and EXT1 was identified as a potential target. The expression and methylation levels of EXT1 were both increased in UCEC tissues and cell lines, as well as elevated EXT1 was closely related to the poor prognosis of patients. Besides, the knockdown of EXT1 significantly inhibited the malignant biological behaviors in UCEC cells. Additionally, the current study also found that the deletion of 1559–2146 bp CpG island segment upregulated EXT1 expression and promoted malignant biological behaviors in UCEC cells. Furthermore, the presence of m7G RNA methylation in UCEC cells also was found. In conclusion, the methylation of EXT1 influenced the gene expression, thereby affecting the malignant biological behaviors in UCEC cells and regulating the pathological progression of UCEC. Graphical
研究领域:
肿瘤学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
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2021
·Vol. 47
·期 6
·2196-2203
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IF 1.73
Lianhua Wang,Qiming Huang,Qingqing Lin,Lvxuan Chen,Qiyang Shi
Aim Endometrial cancer (EC) is a common type of malignant gynecological cancer. Small nucleolar RNA host gene 9 (SNHG9) has been discovered to serve a role in several types of cancer; however, the role of SNHG9 in EC remains unclear. The present study aimed to investigate the effects of lncRNA SNHG9 on cell proliferation and glycolysis in EC cells. Methods SNHG9 and hexokinase 2 (HK2) mRNA expression levels were measured by reverse transcription-quantitative PCR. Glucose consumption and lactate production were detected by the glycolysis cell-based assay kit. Cell Counting Kit-8 and colony formation assays were conducted to detect cell proliferation. The knockdown experiments of SNHG9 and HK2 were carried out by transfection of corresponding small interference RNAs (siRNA). The SNHG9-overexpressed plasmid was transfected into the cells to upregulate SNHG9. HK2 protein levels were analyzed by western blotting assay. Results SNHG9 expression levels were significantly upregulated in EC tissues and cells. The knockdown of SNHG9 subsequently effectively attenuated cell proliferation and glycolysis in vitro, while SNHG9 overexpression reported the opposite effects. Notably, the transfection of 2-DG partially reversed the promoting effect of SNHG9 on glycolysis. Downregulation of HK2 markedly decreased cell proliferation and glycolysis in EC cells antagonized SNHG9. Conclusion Either downregulation of SNHG9 or HK2 inhibits EC cell proliferation and glycolysis via repressing EC cell proliferation and glycolysis.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
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DOI
PubMed
高影响因子
Frontiers in Oncology
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2021
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IF 6.244
Liang Dongxin,Tuo Xiaoqian,Wang Qing,Zhao Lanbo,Zhang Kailu,Wang Yiran,Feng Xue,Yin Panyue,Guo Lin,Liu Yu,Wang Lei,Han Lu,An Ruifang,Li Qiling
The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.
研究领域:
肿瘤学
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医学影像学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLUSTER SCIENCE
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2021
·Vol. 33
·期 6
·2661-2671
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IF 3.061
Chen Ting-ting,Yuan Ming-ming,Tao Yu-mei,Ren Xiao-yan,Li Sufen
Chemotherapy side effects are minimized, and therapeutic results are enhanced by combination therapy, which is extensively utilized in cancer therapy. MTT experiment showed that compared to the free drugs calreticulin (CRT) and gemcitabine (GEM), GEM-CRT@NPs significantly increased the cytotoxicity of endometrial cancer (Ishikawa cells and KLE cells). These drugs were conjugated to a tri-block copolymeric framework. GEM-CRT@NPs were studied using HR-TEM and DLS analysis to determine particle size and zeta potential. Biochemical staining analyses were also used to investigate the morphological characteristics of endometrial cancer cell lines. After KLE and Ishikawa cancer cells were treated with GEM-CRT@NPs, endometrial cell shape was altered, as evidenced by nuclear fragmentation and nuclear condensation (apoptosis hallmarks). Additionally, the most significant apoptosis ratio to mitochondrial membrane potential indicates that the mitochondrial membrane potential is responsible for the cell's death. Upon treatment with GEM-CRT@NPs, systemic toxicity analysis revealed minimal histological abnormalities and significant blood chemistry alterations, and a near-normal look of the organs. Endometrial cancer treatment may be enhanced with the use of the targeted combination therapeutic system.
研究领域:
肿瘤学
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药剂学
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产品关联
DOI
高影响因子
Biomed Research International
·
2021
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IF 3.411
Qin Hu,Shu Zhang,Jun Zhu,Lina Yin,Suping Liu,Xiaowei Huang,Guihao Ke
Endometrial cancer (EC) is a common gynecological malignancy worldwide whose therapy mainly depends on chemotherapy. In past years, an increasing number of studies indicate that hollow MnO2 could serve as a nanoplatform in the drug delivery system. The Brucea javanica oil emulsion (BJOE) has been illustrated to play a vital role in cancers. However, knowledge about the combined effect of H-MnO2-PEG/BJOE in endometrial cancer remains ambiguous up to now. In the present work, we prepared a drug-delivery vector H-MnO2-PEG by chemical synthesis and found that H-MnO2-PEG significantly inhibited cell proliferation in endometrial cancer cells. Moreover, the combination of H-MnO2-PEG/BJOE could repress cell proliferation more efficiently and promote cell apoptosis. Mechanistically, we found that BJOE exerted its role as a promoter of endometrial apoptosis by regulating relative protein expressions. In general, the present study demonstrates that H-MnO2-PEG functions as a critical vector in the tumor microenvironment of endometrial cancer and the significant effect of H-MnO2-PEG/BJOE on cancer cells, suggesting a new paradigm for the treatment of endometrial cancer.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
CELL CYCLE
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2022
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IF 5.173
Tianjiao Lai,Haifeng Qiu,Lulu Si,Yu Zhen,Danxia Chu,Ruixia Guo
Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.
研究领域:
肿瘤学
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分子生物学
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基因组学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
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2017
·Vol. 14
·期 6
·5445-5451
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IF 1.261
Jianxin Zhang,Fengchun Wang,Huali Wang,Yanna Wang,Yan Wu,Hui Xu,Chen Su
Paeoniflorin (PAE), a principal bioactive component of Paeonia lactiflora Pall., appears to have antitumor properties. However, the pharmacological activity of PAE in endometrial cancer and the specific mechanisms have remained largely elusive. The present study aimed to determine the antitumor activity of PAE in the human endometrial cancer cell line RL95‑2 and explore the potential mechanisms. Cell proliferation was assessed to evaluate the antitumor effect of PAE towards RL95‑2 cells via a Cell Counting Kit‑8 assay. Protein expression was examined to investigate changes in the signaling pathways of p38 mitogen‑activated protein kinase (MAPK), c‑Jun N‑terminal kinase (JNK), extracellular signal‑regulated kinase (ERK) and nuclear factor (NF)‑κB in RL95‑2 cells during PAE treatment by western blot analysis. The results revealed that PAE significantly and dose‑ and time‑dependently inhibited the proliferation of RL95‑2 cells. In addition, PAE activated MAPK signaling pathways (p38, JNK and ERK) and the NF‑κB signaling pathway. Furthermore, p38 MAPK and NF‑κB inhibitors (SB203580 and MG‑132, respectively) prevented PAE‑induced proliferative inhibition in RL95‑2 cells. However, ERK and JNK inhibitors (PD98059 and BI‑78D3, respectively) did not produce such an inhibition. In conclusion, the present study demonstrated that PAE exerts its anti‑proliferative activity via activating p38 MAPK and NF‑κB signaling pathways in endometrial cancer cells, providing a potential new drug of choice for endometrial cancer therapy.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Clinical & Translational Oncology
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2022
·Vol. 25
·期 3
·662-672
·
IF 3.34
Chen Jing,Huang Shuting,Li Huawen,Li Yun,Zeng Haishan,Hu Jiemei,Lin Yanchun,Cai Huihua,Deng Pengfei,Song Ting,Guan Tian,Zeng Haoyu,Liu Mubiao
Purpose Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
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2025
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IF 2.9
Biqing Chen,Zengkun Wang,Jiayin Gao,Haizhu Sun,Yinghan Zhao,Yan Liu,Jianyu Liu,Xiaohong Qiu
The occurrence and progression of endometrial cancer are closely associated with metabolic reprogramming, in which polyamine metabolites play a critical role in tumor cell proliferation and invasion. In this study, we developed a label free surface enhanced Raman scattering (SERS) detection platform based on gold nanostars (AuNS), integrated with machine learning algorithms, to achieve highly sensitive detection and precise identification of polyamine metabolites related to endometrial cancer. In complex biological matrices such as serum, the platform yielded stable and reproducible spectral fingerprints, with a detection limit at the nanogram level. Furthermore, by constructing a polyamine metabolite spectral database and introducing machine learning models, both the classification accuracy and AUC values exceeded 95 %, enabling effective discrimination of different metabolic states and mixed systems. Taken together, the AuNS SERS strategy combined with machine learning provides a rapid, non-invasive, and intelligent detection tool for the early diagnosis and metabolic subtyping of endometrial cancer, with significant clinical application potential.
研究领域:
肿瘤学
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代谢组学
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纳米医学
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分子诊断
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转化医学
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妇科肿瘤
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生物分析化学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）