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3 "Gang Zhang"
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Breast cancer
Genomic Characteristics and Its Therapeutic Implications in Breast Cancer Patients with Detectable Molecular Residual Disease
Shu Zhang, Yan Jiang, Lu Zhou, Jing Xu, Gang Zhang, Lu Shen, Yan Xu
Cancer Res Treat. 2024;56(2):538-548.   Published online December 5, 2023
DOI: https://doi.org/10.4143/crt.2023.1059
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Molecular residual disease (MRD) is the main cause of postoperative recurrence of breast cancer. However, the baseline tumor genomic characteristics and therapeutic implications of breast cancer patients with detectable MRD after surgery are still unknown.
Materials and Methods
In this study, we enrolled 80 patients with breast cancer who underwent next-generation sequencing-based genetic testing of 1,021 cancer-related genes performed on baseline tumor and postoperative plasma, among which 18 patients had detectable MRD after surgery.
Results
Baseline clinical characteristics found that patients with higher clinical stages were more likely to have detectable MRD. Analysis of single nucleotide variations and small insertions/deletions in baseline tumors showed that somatic mutations in MAP3K1, ATM, FLT1, GNAS, POLD1, SPEN, and WWP2 were significantly enriched in patients with detectable MRD. Oncogenic signaling pathway analysis revealed that alteration of the Cell cycle pathway was more likely to occur in patients with detectable MRD (p=0.012). Mutational signature analysis showed that defective DNA mismatch repair and activation-induced cytidine deaminase (AID) mediated somatic hypermutation (SHM) were associated with detectable MRD. According to the OncoKB database, 77.8% (14/18) of patients with detectable MRD had U.S. Food and Drug Administration–approved mutational biomarkers and targeted therapy.
Conclusion
Our study reports genomic characteristics of breast cancer patients with detectable MRD. The cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.
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Gastrointestinal cancer
Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner
Pei Cao, Weigang Zhang, Junyi Qiu, Zuxiong Tang, Xiaofeng Xue, Tingting Feng
Cancer Res Treat. 2024;56(1):259-271.   Published online August 16, 2023
DOI: https://doi.org/10.4143/crt.2022.1600
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear.
Materials and Methods
We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC.
Results
Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression.
Conclusion
Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

Citations

Citations to this article as recorded by  
  • WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways
    Fan Huang, Yuchen Wang, XiaoLi Lv, Chenda Huang
    Journal of Bioenergetics and Biomembranes.2024; 56(3): 285.     CrossRef
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  • 170 Download
  • 2 Web of Science
  • 1 Crossref
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Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11
Chenyang Qi, Liping Zou, Suxia Wang, Xing Mao, Yuan Hu, Jiaoyu Shi, Zhigang Zhang, Huijuan Wu
Cancer Res Treat. 2022;54(1):182-198.   Published online March 26, 2021
DOI: https://doi.org/10.4143/crt.2020.578
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied.
Materials and Methods
In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated.
Results
Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells.
Conclusion
Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.

Citations

Citations to this article as recorded by  
  • Deregulated expression of autophagy genes; PIK3C3 and RAB7A in COVID-19 patients
    Mona Tahoun, Ahmed S. Sadaka
    Human Immunology.2024; 85(3): 110801.     CrossRef
  • Prognostic Lysosome-Related Biomarkers for Predicting Drug Candidates in Hepatocellular Carcinoma: An Insilco Analysis
    Junxiu Xu, Kai Zhang, Genhao Zhang
    Journal of Hepatocellular Carcinoma.2023; Volume 10: 459.     CrossRef
  • Targeting VPS34 in autophagy: An update on pharmacological small-molecule compounds
    Yuan Liu, Qilin Yang, Siwei Chen, Zixiang Li, Leilei Fu
    European Journal of Medicinal Chemistry.2023; 256: 115467.     CrossRef
  • RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway
    Zhun Wei, Kezhou Xia, Di Zheng, Changtian Gong, Weichun Guo
    Molecular Medicine.2023;[Epub]     CrossRef
  • The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer
    Chien-An Chu, Yi-Wen Wang, Yi-Lin Chen, Hui-Wen Chen, Jing-Jing Chuang, Hong-Yi Chang, Chung-Liang Ho, Chen Chang, Nan-Haw Chow, Chung-Ta Lee
    International Journal of Molecular Sciences.2021; 22(20): 10964.     CrossRef
  • 6,374 View
  • 225 Download
  • 8 Web of Science
  • 5 Crossref
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