Discover Oncology
·
2024
·Vol. 15
·期 1
·1-13
·
IF 2.8
Yin Xiaoyan,Zhang Haizhong,Wang Jingmiao,Bian Yanrui,Jia Qiaojing,Yang Zhichao,Shan Chunguang
In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
CELL BIOLOGY AND TOXICOLOGY
·
2024
·Vol. 41
·期 1
·1-29
·
IF 5.3
Shang Nan,Zhu Lisi,Li Yan,Song Chengyang,Liu Xiaodan
The prevalence of breast cancer (BRCA) is notable in the female population, being a commonly diagnosed malignancy, where the management of copper levels is crucial for treatment success. This research aims to explore the influence of copper homeostasis on BRCA therapy, with a specific focus on the role of Cyclin-Dependent Kinase 1 (CDK1) and its relationship to copper regulation. A novel thermosensitive hydrogel incorporating nanoparticles (NPs) was engineered to synergize with the chemotherapy drug vincristine (VCR) in inhibiting tumor growth and metastasis. Through a comprehensive approach involving bioinformatics analyses, in vitro experiments, and in vivo models, the study identified CDK1 as a significant factor in BRCA progression under copper homeostasis. MBVP-Gel, a novel thermosensitive hydrogel incorporating NPs, was developed to enhance the delivery of chemotherapy drugs and regulate copper homeostasis in breast cancer treatment. The MBVP-Gel, formulated with copper chelation and VCR NPs, effectively suppressed CDK1 expression, thereby restraining BRCA cell growth and metastasis while enhancing the therapeutic impact of VCR. This investigation offers fresh insights and experimental validation on the interaction between copper homeostasis and BRCA, providing a valuable foundation for refining future treatment strategies. These findings underscore the potential advantages of targeting copper homeostasis and CDK1 in enhancing BRCA therapy, setting the stage for individualized interventions and improved patient consequences.
研究领域:
肿瘤学
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药理学
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纳米技术
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癌症生物学
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DOI
PubMed
高影响因子
CANCER GENE THERAPY
·
2022
·Vol. 29
·期 8
·1217-1227
·
IF 5.854
Wang Zhiwei,Li Mingxing,Liu Yuanfeng,Qiao Zhentao,Yang Ling,Liu Bo,Bai Tao
Autophagy is the predominant self-eating catabolic pathway activated in response to nutrient starvation and hypoxia within the microenvironment of varied malignancies, including hepatocellular carcinoma (HCC). SQSTM1/p62 links its cargos to autophagosomes for degradation, and reportedly acts as a contributor for hepatocarcinogenesis. Five GEO gene microarrays identified corticotropin releasing hormone (CRH) binding protein (CRHBP) as a significantly downregulated gene in HCC (log2 Fold change < −3 and p < 0.001), and an earlier human interactome study indicated that CRHBP may interact with p62. This study aimed to explore (1) the role of CRHBP in HCC development, and (2) whether p62-mediated autophagy was responsible for low CRHBP expression within HCC tissue. Following functional experiments first revealed an anti-proliferative, anti-metastatic, and anti-angiogenic role of CRHBP in HCC cells (Huh-7, Li-7 and HCCLM3) and xenografts. CRHBP negatively regulated cyclin B2 expression, and dissociated cyclin B2-CDK1 complex in HCC cells, thereby leading to cell cycle arrest at G2 phase. To simulate HCC microenvironment in vitro, Huh-7 cells were incubated in Earle’s Balanced Salt Solution (nutrient starvation) or exposed to 1% O 2 (hypoxic exposure). In addition to activating autophagy, nutrient starvation and hypoxic exposure also induced CRHBP degradation. Interestingly, CRHBP was demonstrated as a novel cargo targeted by p62 for degradation in autophagosomes. Blocking autophagy with 3-MA, chloroquine or siSQSTM1 prevented CRHBP degradation in HCC cells. Collectively, our study uncovers a role for CRHBP in retarding HCC development, reducing cyclin B2 expression and impairing cyclin B2-CDK1 interaction. CRHBP downregulation in HCC may attribute to p62-mediated autophagy.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Chuanchuan Lin,Ye He,Qian Feng,Kun Xu,Zhe Chen,Bailong Tao,Xuemin Li,Zengzilu Xia,Hong Jiang,Kaiyong Cai
To control the fate of mesenchymal stem cells (MSCs) in a 3D environment by adjusting the mechanical parameters of MSC-loading scaffolds, is one of the hot topics in the field of regenerative biomaterials. However, a thorough understanding of the relevant MSCs behaviors affected by viscoelasticity , a dynamic physical parameter of scaffolds, is still lacking. Herein, we established an alginate hydrogel system with constant stiffness and tunable stress relaxation rate, which is a key parameter for the viscoelastic property of material. MSCs were cultured inside three groups of alginate hydrogels with various stress relaxation rates, and then RNA-seq analysis of cells was performed. Results showed that the change of stress relaxation rates of hydrogels regulated the most of the different expression genes of MSCs, which were enriched in cell proliferation-related pathways. MSCs cultured in hydrogels with fast stress relaxation rate presented a high self-renewal proliferation profile via activating phosphatidylinositol 3- kinase (PI3K)/protein kinase B (Akt) pathway. In contrast, a slow stress relaxation rate of hydrogels induced MSCs to enter a reversible quiescence state due to the weakened PI3K/Akt activation. Combined with a further finite element analysis , we speculated that the quiescence of MSCs could be served as a positive strategy for MSCs to deal with the matrix with a low deformation to keep stemness. Based on the results, we identified that stress relaxation rate of hydrogel was a potential physical factor of hydrogel to regulate the self-renewal or quiescence of MSCs. Thus, our findings provide a significant guiding principle for the design of MSCs-encapsulated biomaterials.
研究领域:
再生生物材料
·
干细胞生物学
·
生物力学
·
组织工程
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF ONCOLOGY
·
2023
·Vol. 62
·期 5
·1-21
·
IF 5.2
Ting Xue,Yaodong Chen,Jia Xu,Weiqin Du,Pengzhou Kong,Xinri Zhang
Lung cancer is the leading cause of cancer‑related mortality worldwide. Non‑small cell lung cancer (NSCLC) is the most common pathological subtype of lung cancer and is associated with low 5‑year overall survival rates. Therefore, novel and effective chemotherapeutic drugs are urgently required for improving the survival outcomes of patients with lung cancer. Cyclovirobuxine D (CVB‑D) is a natural steroidal alkaloid, used for the treatment of cardiovascular diseases in Traditional Chinese Medicine. Several studies have also demonstrated the antitumor effects of CVB‑D. Therefore, in the present study, the therapeutic effects of CVB‑D in lung cancer and the underlying mechanisms were investigated using the in vivo xenograft model of NSCLC in nude mice and in vitro experiments with the NSCLC cell lines. Bioinformatics analyses of RNA‑sequencing data, and cell‑based functional assays demonstrated that CVB‑D treatment significantly inhibited in vitro and in vivo NSCLC cell proliferation, survival, invasion, migration, angiogenesis, epithelial‑to‑mesenchymal transition and G2/M phase cell cycle. CVB‑D exerted its antitumor effects by inhibiting the KIF11‑CDK1‑CDC25C‑cyclinB1 G2/M phase transition regulatory oncogenic network and the NF‑κB/JNK signaling pathway. CVB‑D treatment significantly reduced the sizes and weights and malignancy of xenograft NSCLC tumors in the nude mice. In conclusion, the present study demonstrated that CVB‑D inhibited the growth and progression of NSCLC cells by inhibiting the KIF11‑CDK1‑CDC25C‑CyclinB1 G2/M phase transition regulatory network and the NF‑κB/JNK signaling pathway. Therefore, CVB‑D is a promising drug for the treatment of NSCLC patients.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Biomed Research International
·
2020
·
IF 2.276
Kiren Mustafa,Hassan Mohamed,Aabid Manzoor Shah,Shaoxuan Yu,Muhammad Akhlaq,Haifang Xiao,Shaoqi Li,Tahira Naz,Shaista Nosheen,Xueyuan Bai,Yuanda Song
Human liver cancer has emerged as a serious health concern in the world, associated with poorly available therapies. The Berberis genus contains vital medicinal plants with miraculous healing properties and a wide range of bioactivities. In this study, different crude extracts of B. lycium Royle were prepared and screened against Human Hepatocarcinoma (HepG2) cell lines. The water/ethanolic extract of B. lycium Royle (BLE) exhibited significant antiproliferative activity against the HepG2 cancer cell line with an IC50 value of 47 μg/mL. The extract decreased the clonogenic potential of HepG2 cells in a dose-dependent manner. It induced apoptotic cell death in HepG2 cells that were confirmed by cytometric analysis and microscopic examination of cellular morphology through DAPI-stained cells. Biochemical evidence of apoptosis came from elevating the intracellular ROS level that was accompanied by the loss of mitochondrial membrane potential. The mechanism of apoptosis was further confirmed by gene expression analysis using RT-qPCR that revealed the decline in Bcl-2 independent of p53 mRNA and a rise in CDK1 while downregulating CDK5, CDK9, and CDK10 mRNA levels at 48 h of BLE treatment. The most active fraction was subjected to HPLC which indicated the presence of berberine (48 μg/mL) and benzoic acid (15.8 μg/mL) as major compounds in BLE and a trace amount of luteolin, rutin, and gallic acid. Our study highlighted the importance of the most active BLE extract as an excellent source of nutraceuticals against Human Hepatocarcinoma that can serve as an herbal natural cure against liver cancer.
研究领域:
药理学
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肿瘤学
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植物学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 21
·10624
·
IF 4.9
Rui-Ze Wu,Bo Zhang,Han-Nong Yu,Qian-Qian Sun,Wen-Xue Yao,Wei-Yang Liu,Jun-Jie Lv,Zhi-Wei Xu,Hong-Qing Qi,Yao Fu,A-Yang Zhao,Yu-Lin Pan,Yong-Hui Wu,Rui Xin
Nickel nanoparticles (NiNPs) are extensively used in nanotechnology, electronics, and biomedical fields, raising concerns about their pulmonary toxicity and potential role in inducing lung adenocarcinoma (LUAD). While heavy metals, like arsenic and cadmium, are well-known to drive LUAD through metabolic reprogramming, the molecular mechanism linking NiNPs to LUAD—particularly their impact on fatty acid metabolism (FAM)—remains unclear. This study is the first to explore whether NiNPs promote LUAD progression via the CDK1/STAT3/FASN axis, a key regulator of FAM, and to evaluate the natural compound apigenin (API) as a potential inhibitory agent. When human (A549) and mouse (LLC) LUAD cells were exposed to NiNPs, assessments of cell function and protein expression revealed increased malignant phenotypes, including enhanced proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), along with activation of the CDK1/STAT3/FASN axis and upregulation of FAM-related markers. Genetic silencing of either CDK1 or FASN reversed the dysregulation of FAM and reduced the malignant characteristics of the cells. Molecular docking analysis confirmed that API binds strongly to CDK1, and further experiments demonstrated that API suppresses NiNP-induced tumor growth both in laboratory cell models and in living organisms, while also blocking the activity of the CDK1/STAT3/FASN axis.
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高影响因子
HISTOLOGY AND HISTOPATHOLOGY
·
2025
·
IF 2
Zhanqiang Zhai,Chunwei Xu,Yonghua Min,Youcai Zhu,Xiaofeng Li
Objectives: The potential treatment option of targeting protein arginine methyltransferase 5 (PRMT5) has been explored, but further investigation is required to assess the efficacy of combination therapy in non-small cell lung cancer (NSCLC). In this study, bioinformatics and online databases were utilized to select the combined therapeutic targets. Methods: The potential kinases associated with PRMT5-related genes in NSCLC were analyzed using The Cancer Genome Atlas (TCGA) database and X2K Appyter (Expression2Kinases) database. In vitro evaluations were conducted to assess the synergistic effects between PRMT5 and cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) cell lines. Results: In our study, CDK1 was primarily the kinase associated with PRMT5-related genes in NSCLC. We observed a significant upregulation of PRMT5 and CDK1 expression in NSCLC tissues. Methylthioadenosine phosphorylase (MTAP)-null NSCLC cell lines demonstrated sensitivity to monotherapy with PRMT5i. A considerable synergistic effect was observed in MTAP-null cells when combining PRMT5i with CDK1i, resulting in the inhibition of cell growth and migration. Conclusion: Our research provides evidence supporting the synergistic anti-tumor effects of targeting PRMT5 and CDK1 in MTAP-deficient NSCLC.
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高影响因子
Frontiers in Veterinary Science
·
2025
·
IF 2.9
Mengjuan Chen,Hui Han,Mengke Qin,Huixin Li,Qiqi Lu,Xin Huang,Qingda Meng,Shanshan Xie
Introduction: Current management of canine mammary tumors (CMTs) remains reliant on surgical resection and chemotherapy. However, these strategies are often limited by high recurrence rates and systemic toxicity. Addressing these limitations requires urgent development of safer and more effective therapeutics. Pseudolaric acid B (PAB), a bioactive compound extracted from the roots of the Pseudolarix kaempferi Gord., has garnered attention for its broad-spectrum antitumor activity and favorable pharmacokinetic profile, and it has shown promise in inhibiting the growth of a variety of tumors, including breast cancer. The aim of this study was to investigate the anticancer effects of PAB on canine mammary tumor U27 cells and its underlying mechanisms.Methods and results: In vitro analyses demonstrated that PAB dose dependently reduced cell viability, suppressed cell proliferation, and triggered caspase-mediated apoptosis. Transcriptomic profiling of PAB-treated tumor cells revealed significant enrichment of differentially expressed genes in pathways such as gap junction, cell cycle, and cellular senescence. Mechanistically, CDK1 suppression by PAB, achieved through binding that diminishes its expression and stability, induced G2/M phase arrest and halted mitotic progression. While these findings suggest the potential of PAB as a candidate for canine mammary tumor treatment, further investigations are warranted to delineate its precise in vivo targeting specificity and pharmacodynamic interactions.Discussion: These findings not only expand the translational applicability of PAB in veterinary oncology but also identify CDK1 as a potential therapeutic vulnerability for combinatorial treatment strategies in CMTs.
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2014
·
IF 7.261
Yang Liu,Yan-Hua Zhu,Cheng-Qiong Mao,Shuang Dou,Song Shen,Zi-Bin Tan,Jun Wang
There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)- b -poly( d , l -lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NP siCDK1 ) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NP siCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer .
研究领域:
肿瘤学
·
分子生物学
·
药学
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纳米技术
·
癌症治疗
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2020
·Vol. 476
·期 2
·513-523
·
IF 2.795
Shan Shuhua,Lu Yang,Zhang Xiaoli,Shi Jiangying,Li Hanqing,Li Zhuoyu
Nature polyphenols widely present in plants and foods are promising candidates in cancer chemotherapy. Emerging evidence has shown that plant polyphenols regulate the expression of miRNAs to exert the anti-Multidrug resistance (MDR) activity, which partly attributes to their regulation on miRNAs methylation. Our previous study found that bound polyphenol from foxtail millet bran (BPIS) had potential as an anti-MDR agent for colorectal cancer (CRC), but its mechanism remains unclear. The present findings demonstrated that BPIS upregulated the expression of miR-149 by reducing the methylation of its CpG islands, which subsequently induced the cell cycle arrest in G2/M phase, resulting in enhancing the chemo-sensitivity of HCT-8/Fu cells. Mechanically, BPIS and its active components (FA and p-CA) reduced miR-149 methylation by inhibiting the expression levels of DNA methyltransferases, promoting a remarkable increase of miR-149 expression. Further, the increased miR-149 induced cell cycle arrest in G 2 /M phase by inhibiting the expression of Akt, Cyclin B1 and CDK1, thus increasing the chemosensitivity of HCT-8/Fu cells. Additionally, a strong inducer of DNA de-methylation (5-aza-dc) treatment markedly increased the chemosensitivity of CRC through elevating miR-149 expression, which indicates the hypermethylation of miR-149 may be the key cause of drug resistance in CRC. The study indicates that the enhanced chemosensitivity of BPIS on CRC is mainly attributed to the increase of miR-149 expression induced by methylation inhibition.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
表观遗传学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Miao Jiefei,Meng Chi,Wu Hongmei,Shan Wenpei,Wang Haoran,Ling Changchun,Zhang Jinlin,Yang Tao
A novel hybrid CHC was designed and synthesized by conjugating β-carboline with an important active fragment N-hydroxyacrylamide of histone deacetylase (HDAC) inhibitor by an amide linkage to enhance antitumor efficacy/potency or even block drug resistance. CHC displayed high antiproliferative effects against drug-sensitive SUMM-7721, Bel7402, Huh7, and HCT116 cells and drug-resistant Bel7402/5FU cells with IC50 values ranging from 1.84 to 3.27 μM, which were two-to four-fold lower than those of FDA-approved HDAC inhibitor SAHA. However, CHC had relatively weak effect on non-tumor hepatic LO2 cells. Furthermore, CHC exhibited selective HDAC1/6 inhibitory effects and simultaneously augmented the acetylated histone H3/H4 and α-tubulin, which may make a great contribution to their antiproliferative effects. In addition, CHC also electrostatically interacted with CT-DNA, exerted remarkable cellular apoptosis by regulating the expression of apoptosis-related proteins and DNA damage proteins in Bel7402/5FU cells, and significantly accumulated cancer cells at the G2/M phase of the cell cycle by suppressing CDK1 and cyclin B protein with greater potency than SAHA-treated groups. Finally, CHC displayed strong inhibitory potency to drug-resistant hepatic tumors in mice. Our designed and synthetic hybrid CHC could be further developed as a significant and selective anticancer agent to potentially treat drug-resistant hepatocellular carcinoma.
研究领域:
药理学
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肿瘤学
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分子生物学
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PubMed
高影响因子
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