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PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1

  • Qing-Chao Zhu , Jian-Hua Sun , Ming-Jun Liang , Zheng-Yun Zhang EMAIL logo and Yang Xia EMAIL logo
Published/Copyright: March 31, 2022

Abstract

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.


Corresponding authors: Zheng-Yun Zhang and Yang Xia, Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China, E-mail: (Z-Y. Zhang), (Y. Xia)

Funding source: National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809

Award Identifier / Grant number: 81974379

  1. Author contributions: Qing-Chao Zhu and Jian-Hua Sun designed the study, supervised the data collection, Ming-Jun Liang analyzed the data, interpreted the data, Zheng-Yun Zhang, Yang Xia prepare the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

  2. Research funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81974379).

  3. Conflict of interest statement: The authors state that there are no conflicts of interest to disclose.

  4. Availability of data and materials: All data generated or analyzed during this study are included in this published article.

  5. Ethics approval: All procedures performed in studies involving human participants were in accordance with the standards upheld by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and with those of the 1964 Helsinki Declaration and its later amendments for ethical research involving human subjects. All animal experiments were approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines.

  6. Informed consent: Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

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Received: 2022-01-14
Accepted: 2022-03-10
Published Online: 2022-03-31
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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