Translational Cancer Research
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2026
·Vol. 15
·期 4
·238
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IF 2.1
Lin Xiang,Tian Peng,Guo-Bin Song,Hou-Qun Ying,Xue-Xin Cheng
Background The cell division cycle-associated ( CDCA ) gene family regulates cell cycle progression and is frequently dysregulated in multiple cancers. However, its roles in tumor stemness maintenance and drug sensitivity remain unclear. This study aimed to investigate the expression of the CDCAs in cancers and their associations with tumor stemness and drug sensitivity, with a particular focus on the effects of CDCA2 on stemness and drug sensitivity in lung and colorectal cancers. Methods CDCA s expression and prognostic value were analyzed using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, while correlations with stemness [DNA methylation-based stemness scores (DNAss) and RNA-based stemness scores (RNAss)] and drug sensitivity [Genomics of Drug Sensitivity in Cancer (GDSC)] were assessed. Functional validation was performed by knocking down CDCA2 in lung and colorectal cancer cell lines. Results Pan-cancer analysis revealed that CDCA s were broadly upregulated across tumor types and were significantly associated with poor prognosis in multiple cancers (P<0.05). Most CDCA s showed positive associations with tumor stemness based on RNAss and DNAss analyses (r>0.3, P<0.05). Drug sensitivity analysis indicated that CDCA expression was closely related to responses to various anticancer agents. Experimental validation demonstrated that CDCA2 knockdown significantly inhibited proliferation of lung and colorectal cancer cells, reduced stemness marker expression, and increased sensitivity to oxaliplatin. Conclusions CDCAs are widely upregulated in cancers and associated with poor prognosis, enhanced tumor stemness, and drug resistance. CDCA2 promotes proliferation and chemoresistance, highlighting its potential as a prognostic biomarker and therapeutic target.
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PLoS One
·
2025
·Vol. 20
·期 7
·e0328000
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IF 2.6
Shuaijun Peng,Ruiqin Sun,Hui Liu,Baoying Wang,Yucheng Li
Gastric mucosal injury can lead to significant gastrointestinal disorders, including inflammation, ulcers, and intestinal metaplasia in severe cases. Although bile acids are known contributors to mucosal damage due to their acidity, the role of chenodeoxycholic acid (CDCA), a primary bile acid, in gastric mucosal injury remains unclear. This study investigates the role of CDCA in inducing gastric mucosal injury and its underlying mechanisms, with a focus on apoptosis and FXR activation, to identify potential therapeutic targets. Mice were administered varying doses of CDCA to evaluate changes in body weight, food intake, and gastric mucosal pathology using hematoxylin-eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) staining. Expression levels of apoptosis-related genes (BAX, BCL-2) and the intestinal metaplasia marker gene (CDX2) were analyzed via RT-PCR and Western blotting (WB). GES-1 cells were treated with different CDCA concentrations to assess cell viability via the CCK-8 assay. Apoptosis rates were measured using flow cytometry, and FXR inhibitors were applied to examine their impact on CDCA-induced effects. CDCA administration in mice resulted in weight loss, reduced food and water intake, gastric epithelial shedding, and intestinal metaplasia. CDCA exposure upregulated Bax and CDX2 expression, while reducing BCL-2 levels. In vitro, CDCA inhibited GES-1 cell viability and increased apoptosis rates, effects that were reversed by FXR inhibition. CDCA induces gastric mucosal injury through apoptosis and FXR activation. These findings provide insights into the mechanisms of bile acid-mediated mucosal damage and highlight FXR as a potential therapeutic target for gastric mucosal disorders.
研究领域:
胃肠病学
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细胞生物学
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分子生物学
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药理学
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病理学
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JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
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2020
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IF 3.813
Xiaofen Zhang,Ziyao Yang,Ziyu Shi,Zijia Zhu,Cai Li,Zhicheng Du,Yiding Zhang,Zipeng Wang,Zhenrui Jiao,Xin Tian,Ji Zhang,Wenlong Zhai,Quancheng Kan
Bile acids (BAs) are currently considered as causative agents for Cholangiocarcinoma (CCA). However, the profile of circulating BAs in CCA have not been well characterized. The aim of this study was to describe the alterations of BAs metabolism in patients with CCA compared to benign biliary diseases (BBD) and healthy controls (HC), and to discover the specific BAs as biomarkers for CCA diagnosis. The concentrations of 15 BAs in plasma were measured in a total of 329 subjects, including patients with BBD, CCA, gallbladder cancer (GC), hepatocellular carcinoma (HCC), and healthy subjects, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Binary logistic regression analysis was used to build a diagnostic model for CCA. An imbalance in the ratio of conjugated to unconjugated BAs was observed in CCA patients compared to BBD and HC groups, with higher conjugated BAs and lower unconjugated BAs. A panel of 2 BA metabolites consisting of CDCA and TCDCA showed high diagnostic performance for CCA versus BBD and CCA versus HC, with higher AUC, sensitivity and specificity than carbohydrate antigen 19−9 (CA 199), clinically employed CCA biomarker. Importantly, HCC and GC samples were also included to confirm specificity of the BA biomarkers for CCA diagnosis. In summary, specific changes in plasma concentrations of BAs may serve as diagnostic biomarkers for distinguishing CCA from BBD and HC, with higher performance than CA199.
研究领域:
肿瘤学
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胃肠病学
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临床化学
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PubMed
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Lipids in Health and Disease
·
2025
·Vol. 24
·期 1
·1-16
·
IF 4.2
Li Lishuang,Ren Xing,Gao Xinyu,Zhao Yujia,Ma Yuman,Gong Junxiao,Yang Shuo,Sun Yanan,Wang Yi
Objective This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives. Methods Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA’s mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism. Results CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters. Conclusion CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.
研究领域:
生物化学
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分子生物学
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药理学
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皮肤科学
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肿瘤学
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内分泌学
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系统生物学
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代谢组学
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转录组学
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蛋白质组学
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JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Zhiyuan Meng,Sen Yan,Wei Sun,Jin Yan,Miaomiao Teng,Ming Jia,Sinuo Tian,Zhiqiang Zhou,Wentao Zhu
As the most commonly used organochlorine pesticide nowadays, chlorothalonil (CHI), is ubiquitous in a natural environment and poses many adverse effects to organisms. Unfortunately, the toxicity mechanisms of CHI have not been clarified yet. This study found that the CHI based on ADI level could induce obesity in mice. In addition, CHI could induce an imbalance in the gut microbiota of mice. Furthermore, the results of the antibiotic treatment and gut microbiota transplantation experiments showed that the CHI could induce obesity in mice in a gut microbiota-dependent manner. Based on the results of targeted metabolomics and gene expression analysis, CHI could disturb the bile acids (BAs) metabolism of mice, causing the inhibition of the signal response of BAs receptor FXR and leading to glycolipid metabolism disorders in liver and epiWAT of mice. The administration of FXR agonist GW4064 and CDCA could significantly improve the CHI-induced obesity in mice. In conclusion, CHI was found to induce obesity in mice by regulating the gut microbiota and BAs metabolism via the FXR signaling pathway. This study provides evidence linking the gut microbiota and pesticides exposure with the progression of obesity, demonstrating the key role of gut microbiota in the toxic effects of pesticides.
研究领域:
毒理学
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微生物学
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代谢学
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药理学
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PubMed
高影响因子
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