Cell Death & Disease
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2026
·Vol. 17
·期 1
·218
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IF 12.2
Zhang Ziyun,Li Yi,Hu Jingjiang,Tang Xingjie,Li Zhanpeng,Sun Xiaoyan,Feng Dade,Yao Yixin,Mao Chao,Tao Yongguang,Xie Li,Luo Huaiqing,Li Yufei,Yu Xing,Peng Xiaoning,Cong Li,Jiang Yiqun
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by poor prognosis, largely attributable to cancer stem cell (CSC) persistence and ferroptosis resistance. However, the molecular mechanisms that coordinately regulate stemness maintenance and ferroptosis suppression in OSCC remain insufficiently characterized. In this study, KIF20A was identified as significantly overexpressed in OSCC and strongly correlated with adverse clinical outcomes. An integrative approach identified DHX9 as a candidate interactor of KIF20A. Mechanistic investigations revealed that KIF20A regulates DHX9 nucleocytoplasmic distribution and inhibits TRIM21-mediated K48-linked polyubiquitination at DHX9-K755, thereby preventing its proteasomal degradation and enhancing protein stability. Elevated DHX9 enhanced SOX2 mRNA stability, leading to upregulation of SOX2, a central regulator of both CSC maintenance and ferroptosis resistance. Functionally, KIF20A promoted CSC phenotypes, inhibited ferroptosis in vitro and in vivo, and activated the PI3K/AKT signaling pathway. Notably, treatment with ENMD-2076 (identified through Connectivity Map analysis) significantly reduced KIF20A expression, attenuated CSC characteristics, augmented cisplatin sensitivity, and exerted marked antitumor activity. These findings elucidate a novel KIF20A-DHX9-SOX2 regulatory axis that simultaneously governs CSC maintenance and ferroptosis evasion in OSCC. Targeting KIF20A, either as a monotherapy or in combination with chemotherapy, may offer a promising strategy to improve therapeutic outcomes in OSCC.
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PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Songtao Li,Tianxing Lv,Xiaxia Fan,Mangmang Feng,Meng Zhou,Zhuoyu Li
Background Chemotherapy remains the main treatment for colon cancer, but the development of resistance has limited its efficacy. There is an urgent need to exploit a more effective therapeutic strategy. Alpha-linolenic acid (ALA), as an essential nutrient for the human body, has been found to increase the therapeutic effect of chemotherapy drugs. Purpose Exploring the potential mechanism of alpha linolenic acid reversing chemotherapy resistance in colon cancer. Results ALA reverses chemoresistance in colorectal cancer and suppresses stemness in resistant colorectal cancer cells. SPP1 functions as a key mediator in ALA-induced reversal of chemoresistance; its downregulation disrupts the interaction with the downstream receptor CD44, thereby mitigating chemotherapy resistance. Subsequently, ALA inhibits the expression of SOX2, a transcription factor that promotes SPP1 transcription. Further analysis revealed that decreased SPP1 expression leads to reduced levels of FAP, a marker of cancer-associated fibroblasts (CAFs), and that a functional interaction exists between SPP1 and FAP. Interestingly, ALA disrupted the interaction between SPP1 and FAP, thereby preventing CAFs accumulation. In vivo studies confirmed that ALA reverses colorectal cancer chemoresistance via the SOX2/SPP1/FAP signaling axis. Conclusion The study demonstrates that ALA in quinoa depresses the stemness of colorectal cancer and reduces the number of CAFs via SPP1, thereby reversing chemotherapy resistance. These findings highlight ALA as a promising dietary-based adjuvant for enhancing chemotherapy efficacy in colorectal cancer and provide new mechanistic insights into targeting tumor stemness and stromal remodeling.
研究领域:
肿瘤学
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分子生物学
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营养与癌症
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转化医学
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肿瘤微环境
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干细胞生物学
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PubMed
高影响因子
Frontiers in Oncology
·
2026
·
IF 3.4
Yang Liu,Yuefen Wang,Cuimei Zhao,Wenbo Li,Zongmin Ma,Chen Wang,Zhongxia Yuan,Shaomin Wang,Nan Zhang,Yangang Wang
ObjectiveGastric cancer (GC) and its precursor chronic atrophic gastritis (CAG) exhibit a high comorbidity with depression. However, the core molecular mechanisms underlying stomach-brain axis-mediated crosstalk between GC/CAG and depression remain poorly clarified. This study attempted to screen pivotal molecules correlated with the bidirectional correlation between GC/CAG and depression, and explore the inflammatory regulatory network through integrated bioinformatics analysis and systematic in vivo and in vitro validation, so as to provide potential clues for revealing their interactive relationship.MethodsWe integrated transcriptomic datasets of CAG, GC, and depression to identify shared differentially expressed genes, further prioritized core diagnostic genes by machine learning, and characterized their biological functions through functional enrichment analysis. In vivo validation was performed in MNNG-induced CAG/GC rat models, including behavioral tests, histopathological evaluation, and gene expression analysis of gastric and brain tissues. Molecular docking and molecular dynamics simulations were performed to assess the binding affinity and structural stability between MNNG and SOX2. In vitro experiments explored how SOX2 expression levels correlate with NOTCH signaling/IL-6 in gastric epithelial cells and paracrine effects on neuronal inflammation.ResultsA total of 21 overlapping differentially expressed genes were screened out, among which 8 core diagnostic genes with AUC values greater than 0.7 were identified, and SOX2 presented the highest diagnostic efficiency with an AUC of 0.849. The MNNG-induced model rats displayed reduced activity and anhedonia-like behavior, accompanied by decreased SOX2 expression and activated NOTCH/IL-6 signaling in gastric and brain tissues. Molecular docking results confirmed that the binding energy between MNNG and SOX2 was −5.5 kcal/mol. In vitro cellular assays revealed an association between SOX2 downregulation and NOTCH cascade activation alongside elevated IL-6 secretion; neuronal cells cultured with gastric cancer cell-derived conditioned medium exhibited concurrent IL-6-related inflammatory alterations.ConclusionThis study characterizes the bidirectional correlative relationship between GC/CAG and depression mediated by the stomach-brain axis. SOX2 is characterized as a key molecule correlated with the regulation of the NOTCH/IL-6 signaling pathway in this interactive network, indicating its potential as a diagnostic biomarker and therapeutic target for GC/CAG complicated with depression.
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
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IF 5.714
Shu-ping Yang,Qing Su,Ya-ru Zhang,Yun Sun,Yu-rong Chai
As the main lymphoid organ, the thymus degenerates with age. The loss of thymic epithelial cells is mainly related to thymus degeneration and reduced T cells development. As an insulin sensitizer, metformin is a first-line drug for the treatment of diabetes and has been shown to prolong the lifespan of mice, but the mechanism is still unclear. In this study, we explored the therapeutic effect of metformin on thymus degeneration in the accelerated aging mice, which was established by intraperitoneal injection D-galactose (120 mg/kg/day) for eight weeks. Metformin was intragastrically given with 100 or 300 mg/kg body weight per day, respectively, for six weeks. Histological examination showed that metformin administration could alleviate thymus atrophy caused by D-galactose. In addition, metformin therapy increased mitochondrial membrane potential, with a reduction in mitochondrial reactive oxygen species, MDA and SOD levels, and restored mitochondrial balance through enhanced expression of dynamin-related protein 1 (Drp1). Furthermore, metformin altered T lymphocyte subsets and cellular senescent cells; the expression of FoxN1, Aire and Sox2 of thymic epithelial cells also increased. Thus, metformin presented a positive effect on thymic degeneration through improving mitochondrial function. Taken together, these findings revealed an unexpected complexity in the anti-aging of this widely used drug.
研究领域:
药理学
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免疫学
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老年学
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细胞生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2016
·Vol. 37
·期 4
·998-1004
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IF 2.348
Yang Li,Zhenqing Wei,Bin Dong,Zhigang Lian,Yinghui Xu
Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is secreted by tumors and influences tumor growth and metastasis. In order to investigate the effects of silencing PGI/AMF on the migration and the sphere forming abilities of human glioblastoma U87 cells, as well as on the side population cells (SPCs), PGI/AMF was silenced using siRNA. Western blot analysis and RT-qPCR were used to assess the expression of PGI/AMF, Akt and SRY (sex determining region Y)-box 2 (SOX2). Wound healing, migration and tumorsphere formation assays were performed to assess invasion and metastatic potential. The proportion of SPCs was determined using Hoechst 33342 dye and flow cytometric analysis. PGI/AMF silencing inhibited the wound healing capacity and migration ability of U87 cells by 52.6 and 80.4%, respectively, compared with the scrambled siRNA (both P<0.001). Silencing of PGI/AMF decreased the proportion of SPCs in the U87 cells by 80.9% (P<0.01). The silencing of PGI/AMF decreased the number and size of tumorspheres by 53.1 and 39.9%, respectively, compared with the scrambled siRNA (both P<0.01). The silencing of PGI/AMF decreased the levels of phosphorylated Akt (-71.9%, P<0.001) compared with the scrambled siRNA, as well as the levels of the stemness marker, SOX2 (-61.7%, P<0.01). Taken together, these findings suggest that PGI/AMF silencing decreases migration, tumorsphere formation as well as the proportion of SPCs in glioblastoma U87 cells. We suggest that the Akt pathway is involved, and our results provide a potential new target for the treatment of glioblastoma.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2014
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IF 2.305
Deependra Tyagi,Javier Batista Perez,Amita Nand,Cheng Zhiqiang,Peizhe Wang,Jie Na,Jingsong Zhu
Surface plasmon resonance imaging (SPRi) has emerged as a versatile biosensor to detect a wide range of biomolecular interactions with divergent potential applications. However, the use of this advanced-level technology for stem cell lysate study is still not much explored. Cell lysates are significant biological analytes used for disease diagnostics and proteomic studies, but their complex nature limits their use as an analyte for SPRi biosensors. Here, we review the problems associated with the use of SPRi for stem cell lysate study and examine the role of surface chemistry, running buffer, and blocking solution in order to minimize nonspecific adsorption (NSA). We detect the expression of Oct4, Sox2, Nanog , Rex1 , and Lin28 biomarkers present in mouse embryonic stem cell (mESC) lysate against their corresponding antibodies immobilized on the sensor surface with reduced NSA. The current study shows that the conjunction of SPRi and microarray can be used as a label-free, high-throughput, and rapid technique for detection of biomarkers and their relative abundance in stem cell lysate study.
研究领域:
生物传感
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干细胞生物学
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蛋白质组学
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分析化学
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生物技术
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
·
IF 7.419
Mohsen Sheykhhasan,Razieh Amini,Sara Soleimani Asl,Massoud Saidijam,Seyed Mahmoud Hashemi,Rezvan Najafi
Alzheimer's disease (AD) is a degenerative disease that causes memory and learning impairments as well as dementia. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with AD. This study investigated the effects of drug delivery of COQ10 by exosomes derived from adipose-derived stem cells (ADSCs-Exo) on cognition, memory, and neuronal proliferation in a rat model of Streptozotocin (STZ)-induced AD. Since the establishment of the AD model, the rats have received intraperitoneal injections of CoQ10, Exo, or CoQ10-loaded ADSCs-Exo (Exo+ CoQ10). The passive avoidance test and the Morris water maze (MWM) were used to assess memory and cognition changes. Cell density was determined using histological methods. The expression of BDNF was measured using an ELISA kit. SOX2 expression was determined using immunohistochemistry. According to the results of the MWM and passive avoidance task, Exo+CoQ10 significantly improved STZ-induced memory impairment compared to CoQ10 and Exo groups alone. Furthermore, BDNF expression increased in the STZ-induced rats after Exo+ CoQ10, when compared to the CoQ10 and Exo groups. In addition, Exo+CoQ10 had the highest cell density and SOX2 gene expression, when compared to the CoQ10 and Exo groups. According to the findings of this study, Exo+ COQ10 enhanced cognition and memory deficiency in Alzheimer's disease by boosting BDNF and SOX2 levels in the hippocampus. Hence, the use of exosomes derived from adipose-derived stem cells as the carrier of CoQ10 may increase the therapeutic effect of CoQ10, which can possibly be due to the regenerative properties of the exosomes.
研究领域:
神经科学
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药理学
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干细胞研究
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神经退行性疾病
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PubMed
高影响因子
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