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Association of Jagged1 expression with malignancy and prognosis in human pancreatic cancer

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Abstract

Purpose

Pancreatic cancer is one of the most aggressive cancers. Preclinical and clinical data indicate that Notch 1 ligand jagged1 (JAG1) plays a pro-oncogenic role in several malignant cancers. As yet, however, the role of JAG1 in pancreatic cancer is poorly understood. The objective of the present study was to investigate JAG1 as a therapeutic target in human pancreatic cancer.

Methods

Expression levels of Notch signaling molecules were assessed using GEO datasets and Western blot analysis, respectively. Anti-tumor effects following JAG1 silencing were evaluated using in vitro and in vivo assays. Prognostic implications were assessed using GEO datasets.

Results

Using GEO datasets and Western blot analysis we detected significantly higher JAG1 mRNA and protein expression levels in pancreatic cancer compared to normal pancreatic tissues. JAG1 silencing significantly restrained the growth, migration and invasion of pancreatic cancer cells through the induction of apoptosis and blockade of various kinases independent of the Notch1 pathway. Combined JAG1 silencing and gemcitabine treatment showed synergistic anti-viability effects in human pancreatic cancer cells. JAG1 silencing also resulted in significant anti-cancer effects in vivo and high JAG1 expression was found to be associated with an adverse prognosis in pancreatic cancer patients.

Conclusions

From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer.

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03033899) and (2016R1A6A1A03012862).

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Authors and Affiliations

  1. Department of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju-do, 63243, Republic of Korea

    Jungwhoi Lee & Jae Hoon Kim

  2. Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea

    Jungsul Lee

  3. Subtropical/tropical Organism Gene Bank, Jeju National University, Jeju-do, 63243, Republic of Korea

    Jae Hoon Kim

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  1. Jungwhoi Lee
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  2. Jungsul Lee
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Contributions

JW Lee conceived and supervised the experiments. JW Lee and JS Lee designed and performed the experiments. JS Lee performed the gene expression profiling and survival analyses. JW Lee, J Lee and JH Kim analyzed the data. JW Lee and JH Kim obtained the funding. JW Lee wrote and proofread the manuscript.

Corresponding authors

Correspondence to Jungwhoi Lee or Jae Hoon Kim.

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All experiments were approved by the Institutional Ethics Committee of the Jeju National University.

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None declared.

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Lee, J., Lee, J. & Kim, J.H. Association of Jagged1 expression with malignancy and prognosis in human pancreatic cancer. Cell Oncol. 43, 821–834 (2020). https://doi.org/10.1007/s13402-020-00527-3

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