4.7 Article

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

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CELL DEATH & DISEASE
卷 11, 期 4, 页码 -

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SPRINGERNATURE
DOI: 10.1038/s41419-020-2475-3

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资金

  1. Innovation Capability Development Project of Jiangsu Province [BM2015004]
  2. National Natural Science Foundation of China [81871980, 81572337, 81672449]
  3. Priority Academic Program AQ3 Development of Jiangsu Higher Education Institutions (PAPD) [JX10231801]
  4. NationalScienceFoundationforYoungScientistsofChina [81902455]
  5. Project of Invigorating Health Care through Science, Technology, and Education, Jiangsu Provincial Medical Outstanding Talent [JCRCA2016009]
  6. Jiangsu Key Medical Discipline (General Surgery) [ZDXKA2016005]

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Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and high mortality. However, the biological role of miR-548t-5p in PC has not been reported. In this study, we found that miR-548t-5p expression was significantly decreased in PC tissues compared with adjacent tissues, and that low miR-548t-5p expression was associated with malignant PC behavior. In addition, high miR-548t-5p expression inhibited the proliferation, migration, and invasion of PC cell lines. Regarding the molecular mechanism, the luciferase reporter gene, chromatin immunoprecipitation (ChIP), and functional recovery assays revealed that YY1 binds to the miR-548t-5p promoter and positively regulates the expression and function of miR-548t-5p. miR-548t-5p also directly regulates CXCL11 to inhibit its expression. A high level of CXCL11 was associated with worse Tumor Node Metastasis (TNM) staging in patients with PC, enhancing proliferation and metastasis in PC cells. Our study shows that the YY1/miR-548t-5p/CXCL11 axis plays an important role in PC and provides a new potential candidate for the treatment of PC.

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