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An Analysis Regarding the Association Between DAZ Interacting Zinc Finger Protein 1 (DZIP1) and Colorectal Cancer (CRC)

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Abstract

Colorectal cancer (CRC) is the third most common malignant disease worldwide, and its incidence is increasing, but the molecular mechanisms of this disease are highly heterogeneous and still far from being fully understood. Increasing evidence suggests that fibrosis mediated by abnormal activation of fibroblasts based in the microenvironment is associated with a poor prognosis. However, the function and pathogenic mechanisms of fibroblasts in CRC remain unclear. Here, combining scrna-seq and clinical specimen data, DAZ Interacting Protein 1 (DZIP1) was found to be expressed on fibroblasts and cancer cells and positively correlated with stromal deposition. Importantly, pseudotime-series analysis showed that DZIP1 levels were up-regulated in malignant transformation of fibroblasts and experimentally confirmed that DZIP1 modulates activation of fibroblasts and promotes epithelial-mesenchymal transition (EMT) in tumor cells. Further studies showed that DZIP1 expressed by tumor cells also has a driving effect on EMT and contributes to the recruitment of more fibroblasts. A similar phenomenon was observed in xenografted nude mice. And it was confirmed in xenograft mice that downregulation of DZIP1 expression significantly delayed tumor formation and reduced tumor size in CRC cells. Taken together, our findings suggested that DZIP1 was a regulator of the CRC mesenchymal phenotype. The revelation of targeting DZIP1 provides a new avenue for CRC therapy.

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Data Availability

The data and materials in the current study are available from the corresponding author: Wei Huang: huangwei87nj@163.com and Xiao-ping Qian: 20223053@njucm.edu.cn.

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Funding

The present study was supported by Nanjing Medical Key Foundation (Grant No. ZKX21028), Jiangsu Province Chinese medicine science and technology development key projects (Grant No. ZD202227), and Jiangsu Province Natural Science Foundation Program (Grant No. BK20211007).

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Author notes

  1. Yu Zhang and Yuan-jie Liu have contributed equally to this work.

Authors and Affiliations

  1. Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, China

    Yu Zhang & Xiao-ping Qian

  2. Department of Medical Oncology, Affiliated Jinling Hospital, Medical School Nanjing University, Nanjing, 210029, Jiangsu, China

    Yu Zhang & Zhao-xu Yang

  3. Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China

    Yuan-jie Liu

  4. Department of Pathology, Affiliated Jinling Hospital, Medical School Nanjing University, Nanjing, 210029, Jiangsu, China

    Jia Mei

  5. Department of Oncology, Nanjing Tianyinshan Hospital, Nanjing, 211199, Jiangsu, China

    Yu Zhang

  6. Comprehensive Cancer Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Clinical Cancer Institute of Nanjing University, Nanjing, 210008, Jiangsu, China

    Xiao-ping Qian

  7. Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Hanzhong Road No.155, Nanjing, 210029, Jiangsu, China

    Wei Huang

Authors
  1. Yu Zhang
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Contributions

YZ and Y-jL drafted the manuscript and performed all experiments, JM selected collected histological samples and reviewed histological samples, Z-xY assistance in the animal experiments and analyzed the data. X-pQ and WH provided the research funding. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Xiao-ping Qian or Wei Huang.

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Competing Interest

The authors declare no conflicts of interest. All authors contributed to data analysis, drafting, or revising of the article; agree on the journal to which the article is being submitted; provided final approval of the version to be published; agree to be accountable for all aspects of the work.

Ethical Approval

This study was conducted according to the ethical standards contained in the Declaration of Helsinki, and in national and international guidelines. The study’s protocol was approved by the ethics committee of the Jiangsu Province Hospital of Chinese Medicine, and informed consent was obtained from clinicians and patients (2021NL-206-01).

Consent to Participate

Written information was provided and written consent was given to all participants prior to collection of specimens for research purposes. All mouse experiments were performed by the Guide for Care and Use of Laboratory Animals and approved by the Animal Ethics Committee of Jiangsu Province Hospital of Chinese Medicine (2022DW-10-01). Before data collection, the first author obtained written consent from all participants concerning participation and subsequent publication of the study results.

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Zhang, Y., Liu, Yj., Mei, J. et al. An Analysis Regarding the Association Between DAZ Interacting Zinc Finger Protein 1 (DZIP1) and Colorectal Cancer (CRC). Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01065-1

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