CELLULAR SIGNALLING
·
2025
·
IF 3.7
Qingqing Chen,Ling Ouyang
Recent findings have indicated that the F-box E3 ubiquitin ligase, F-box only protein 11 (FBXO11), may serve a tumor-suppressing role in certain types of cancers. However, its specific function in ovarian cancer (OC) remains to be elucidated. This study revealed that FBXO11 expression is reduced in OC tissues compared to normal tissues. To assess the role of FBXO11 in OC cells, we established stable human OC cell lines with tetracycline-inducible (Tet-on) expression of FBXO11 CDS or shRNA. FBXO11 inhibited OC cell proliferation, colony formation, migration, invasion, and cell cycle transition from G0/G1 to S phase in vitro . Moreover, FBXO11 suppressed xenograft tumor growth in mice in vivo . Concurrently, FBXO11 reduced the volume of ascites and the number of metastatic tumor nodules in the peritoneal metastasis model. Mechanistically, FBXO11 promoted kinesin family member 2C (KIF2C) to undergo K48-linked ubiquitination and proteasomal degradation, and KIF2C knockdown reversed the tumor-promoting function of FBXO11 downregulation. Additionally, we demonstrated that FBXO11 is a transcriptional target of zinc-finger protein 217 (ZNF217), a known transcriptional repressor that has been implicated in the promotion of OC progression and the prediction of poor prognosis. In summary, FBXO11 functions as a tumor suppressor in OC through ubiquitin-proteasomal degradation of KIF2C; and the low expression level of FBXO11 in OC may be attributed to its transcriptional inhibition by transcription factor ZNF217. These findings provided new insights into understanding the molecular mechanism of OC progression.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PATHOLOGY RESEARCH AND PRACTICE
·
2022
·
IF 3.309
Jianfa Wu,Xiaohong Ni,Zhen Yu,Suqin Wu,Zhou Liu
Background CRNDE is known to be an important predictive factor of prognosis in many tumors; however, its role in cisplatin resistance is still unknown in ovarian cancer. The aim of the current research was to investigate the association between CRNDE and cisplatin resistance. Materials and methods QRT-PCR and in situ hybridization assay were employed to detect the expression of CRNDE in ovarian cancer cells and tissues; CCK8 assay, AnnexinV-FITC apoptosis assay and Trans-well assay, to determine the cell proliferation , apoptosis and invasion; and RNA-pull down assay, mass spectrometry analysis, gene microarray to search the targeted gene of CRNDE and SRSF1 . Association of CRNDE with SRSF1 was determined in ovarian cancer cells and nude mice . Results It was found that CRNDE and SRSF1 expression were higher in the cisplatin resistant ovarian cancer cells than their control cells. High expression of CRNDE and SRSF1 led to cisplatin resistance. While inhibition of CRNDE or SRSF1 sensitized ovarian cancer to cisplatin in vitro and in vivo. Moreover, as indicated in RIP assay, SRSF1 was potentially the targeted gene of CRNDE, and CRNDE promoting SRSF1 expression to induce cisplatin resistance; as indicated in gene microassay, there was significantly positive correlation between SRSF1 and TIA1 , and SRSF1 promoting TIA1 expression. Conclusion In conclusion, CRNDE induced cisplatin resistance in ovarian cancer through SRSF1/TIA1 signaling pathway ; thus, CRNDE inhibitor or SRSF1 inhibitor combined with cisplatin might act as a novel promising approach to ovarian cancer.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
·
IF 6.353
Wang Qiaoying,Wu Changqiang,Li Xiaoting,Yang Dixiao,Shi Liangjun
We have designed and developed an effective drug delivery system using biocompatible polymer of poly (ethylene glycol)-polyaspartic acid (mPEG-PAsp) for co-loading the chemotherapy drugs paclitaxel (PTX) and cisplatin (CP) in one nano-vehicle. This study aimed to improve the anti-cancer efficacy of combinations of chemotherapy drugs and reduce their side effects. mPEG-PAsp-(PTX/Pt) nano-micelles disperse well in aqueous solution and have a narrow size distribution (37.8 ± 3.2 nm) in dynamic light scattering (DLS). Drug release profiles found that CP released at pH 5.5 was significantly faster than that at pH 7.4. MPEG-PAsp-(PTX/Pt) nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 μg/mL. Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms. Results from our studies suggested that mPEG-PAsp-(PTX/Pt) nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Qingrong Li,Xiaoyuan Yang,Xuelin Xia,Xiao-Xia Xia,Deyue Yan
Recombinant elastin-like polypeptides (ELPs) have emerged as an attractive nanoplatform for drug delivery due to their tunable genetically encoded sequence, biocompatibility, and stimuli-responsive self-assembly behaviors. Here, we designed and biosynthesized an HER2 (human epidermal growth factor receptor 2)-targeted affibody–ELP fusion protein (Z-ELP), which was subsequently conjugated with monomethyl auristatin E (MMAE) to build a protein–drug conjugate (Z-ELP-M). Due to its thermal response, Z-ELP-M can immediately self-assemble into a nanomicelle at physiological temperature. Benefiting from its active targeting and nanomorphology, Z-ELP-M exhibits enhanced cellular internalization and deep tumor penetration in vitro. Moreover, Z-ELP-M shows excellent tumor targeting and superior antitumor efficacy in HER2-positive ovarian cancer, demonstrating a relative tumor growth inhibition of 104.6%. These findings suggest that an affibody-functionalized elastin-like peptide–drug conjugate nanomicelle is an efficient strategy to improve antitumor efficacy and biosafety in cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2023
·Vol. 19
·期 12
·2045-2059
·
IF 2.9
Yang Bowen,Huang Luyao,Zhou Zishuo,Yin Shanmei,Xi Mingrong
We aimed to develop an ovarian cancer-directed drug delivery system based on the high affinity of hyaluronic acid for CD44. The effects and mechanisms of hyaluronic acid-containing nanoparticles were investigated. The expression of CD44 in ovarian cancer was also determined. Hyaluronic
acid polymerized nanoparticles (HANPs), FITC-HANPs, and paclitaxel (PTX)-HANPs were prepared, and their characteristics were evaluated. The in vitro targetability and cytotoxicity properties of PTX-HANPs were evaluated through in vitro drug uptake and cytotoxicity assays. The
mechanisms of PTX-HANPs activity were investigated by apoptosis, wound healing, and Transwell invasion assays. In vivo targeting properties of HANPs were observed using a mouse ID8 subcutaneous model. in vitro experiments revealed an improved uptake of FITC-HANPs. The cytotoxicity
of PTX-HANPs in A2780/CP70 and ID8 cells was higher than that of PTX alone. PTX-HANPs increased cell apoptosis in a dose-dependent manner and exhibited a similar ability as PTX to inhibit cell migration. Furthermore, HANPs did not promote A2780/CP70 or ID8 cell migration and showed limited
inhibitory effects on their invasion. In vivo drug tracing experiments demonstrated the targetability of FITC-HANPs. In conclusion, PTX-HANPs improved PTX targetability and exhibited potent tumor-specific therapeutic activities. It may be considered a promising formulation for the preclinical
development of agents targeting epithelial ovarian cancer.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
高影响因子
SENSORS
·
2025
·Vol. 25
·期 11
·3347
·
IF 3.5
Bei Wang,Gengyu Liang,Lingqin Meng,Han Li,Zishuo Song,Yang Xu,Yonghong He,Deling Duan,Qiuxia Shi,Tian Guan,Ya Gong
Simultaneous detection of multiple biomarkers is essential for effective cancer screening. Taking ovarian cancer as an example, the combined detection of CA125 and HE4 has proven to be the most efficient and accurate among multiple biomarker combinations. In this study, we proposed a dual immunosensor based on weak value amplification (WVA) to detect ovarian cancer. By modifying the sensor surface through a self-assembled monolayer technique and utilizing recombinant protein G for antibody enrichment and directional capture, the sensor enables high-precision, simultaneous detection of CA125 and HE4, with detection limits of 5.39 U/mL and 1.79 ng/mL, respectively. Furthermore, the sensor demonstrates excellent specificity, effectively distinguishing target analytes from non-target molecules. This study provides a novel approach for early cancer screening and clinical diagnosis, highlighting the potential of WVA-based immunosensors in ovarian cancer detection.
研究领域:
生物医学工程
·
肿瘤学
·
诊断技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2011
·Vol. 6
·期 9
·e25433
·
IF 4.411
Lihua Cheng,Chengmeng Jin,Wen Lv,Qiuping Ding,Xu Han
Background
Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired.
Methodology/Principal Findings
Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) copolymers (PLGA-mPEG). The nanoparticles have an average diameter of approximately 80 nm measured by transmission electron microscope (TEM). The encapsulation efficiency of cisplatin in the nanoparticles is up to 72%. Meanwhile, we have also observed a controlled release of cisplatin in a sustained manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles against IGROV1-CP cells. Moreover, the median lethal dose (LD 50 ) of the cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous administration, which was much higher than that of free cisplatin.
Conclusion
This developed cisplatin-loaded nanoparticle is a promising formulation for the delivery of cisplatin, which will be an effective therapeutic regimen of ovarian cancer without severe side effects and cumulative toxicity.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Weiyuan Lyu,Xinrui Cheng,Ziqing Yu,Ruirui Dong,Zheyi Sheng,Ting Zhang,Xia Yin,Feng Shen
Ovarian cancer (OC) is one of the three major gynecologic malignancies and has the highest mortality rate because of the late diagnosis. Liquid biopsy based on serum protein biomarkers has demonstrated great potential for early diagnosis but remains limited by the analysis performance of conventional immunoassay technologies, such as chemiluminescence, and biomarkers, such as CA125. To address this challenge and achieve accurate early-stage diagnosis of OC, we developed a digital immunoassay on a SlipChip (DiSC) for quantitative analysis of a potential serum protein biomarker, Spondin-1 (SPON1). The DiSC system achieved a limit of detection (LoD) of 23 fg/μL for digital quantification of SPON1. The DiSC system was utilized to quantify the serum level of SPON1 in 357 clinical serum samples, including 63 from patients with benign ovarian tumors and 294 from patients with malignant ovarian cancer, ranging from stages I to IV. SPON1 concentrations were significantly different in samples from patients with malignant ovarian cancer. Notably, significantly different SPON1 levels were observed in early stages (I and II), in lymph node-negative cases (N 0 ), and before metastasis (M 0 ), suggesting that SPON1 could serve as a sensitive diagnostic biomarker for early-stage OC. The differential diagnostic model based on SPON1 levels quantified using DiSC demonstrated an area under the curve (AUC) of 0.8187 for early-stage OC, a significant improvement over CA-125 (AUC = 0.6967). For OC of all stages, the AUC was 0.8225, which could be further increased to 0.8750 when combined with CA-125. This showcases the potential of SPON1 as a novel biomarker for sensitive early-stage diagnosis of ovarian cancer and the capability of the DiSC system in discovering low-abundance biomarkers for disease diagnosis.
研究领域:
肿瘤学
·
生物医学工程
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2024
·Vol. 7
·期 1
·1-15
·
IF 5.2
Gong Ting-Ting,Liu Fang-Hua,Xiao Qian,Li Yi-Zi,Wei Yi-Fan,Xu He-Li,Cao Fan,Sun Ming-Li,Jiang Feng-Li,Tao Tao,Ma Qi-Peng,Qin Xue,Song Yang,Gao Song,Wu Lang,Zhao Yu-Hong,Huang Dong-Hui,Wu Qi-Jun
Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Luhai Wang,Nana Wang,Lin Deng,Chao Min,Yi Kang,Tingting Bai,Guodong Zhao,Mengdong Yang,Yefei Zhu,Yu Zhang
Simultaneous analysis of multiple protein and nucleic acid biomarkers in one clinical sample can provide clinically valuable results for the diagnosis, monitoring, and management of diseases. However, current diagnostic platforms primarily rely on the independent detection of proteins and nucleic acids, which is time-consuming and labor-intensive. In this study, we propose a microfluidic chip system that integrates microfluidic molecular Point-of-Care Testing (POCT) technology and microfluidic homogeneous chemiluminescence analysis (CLIA) technology for simultaneous detection of protein and nucleic acid biomarkers of ovarian cancer (OC). The integrated system shows good detection limits of 10 fM for miR-92a and 15 pM for HE4. In primary clinical tests with human samples, the diagnostic sensitivity and specificity of the simultaneous detection of two biomarkers (miR-92a and HE4) for OC were 100 % and 96.1 %, respectively, and the area under the curve (AUC) was 0.996. Therefore, the combined evaluation of multiple biomarkers of different dimensions can improve the specificity and sensitivity of diagnosis. This system can also be applied to other tumor markers and biomarkers in other fields of diseases, offering a broad spectrum of diagnostic capabilities.
研究领域:
医学诊断
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Yang Feng,Zhao Ziyu,Cai Shaoyi,Ling Li,Hong Leying,Tao Liang,Wang Qin
Carboplatin resistance in ovarian cancer (OV) is a major medical problem. Thus, there is an urgent need to find novel therapeutic targets to improve the prognosis of patients with carboplatin-resistant OV. Accumulating evidence indicates that the gene COL1A1 (collagen type I alpha 1 chain) has an important role in chemoresistance and could be a therapeutic target. However, there have been no reports about the role of COL1A1 in carboplatin-resistant OV. This study aimed to establish the detailed molecular mechanism of COL1A1 and predict potential drugs for its treatment. We found that COL1A1 had a pivotal role in carboplatin resistance in OV by weighted gene correlation network analysis and survival analysis. Moreover, we constructed a competing endogenous RNA network (LINC00052/SMCR5-miR-98-COL1A1) based on multi-omics data and experiments to explore the upstream regulatory mechanisms of COL1A1. Two key pathways involving COL1A1 in carboplatin resistance were identified by co-expression analysis and pathway enrichment: the “ECM-receptor interaction” and “focal adhesion” Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, combining these results with those of cell viability assays, we proposed that ZINC000085537017 and quercetin were potential drugs for COL1A1 based on virtual screening and the TCMSP database, respectively. These results might help to improve the outcome of OV in the future.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 7
·883-892
·
IF 2
Xiaoyu Yu,Chun Du,Yifei Cui,Yang Jiang,Di Feng
Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased β-catenin expression and inhibited the activation of Wnt/β-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (−2005–+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of β-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
✓ 已验证
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）