4.8 Article

Nanomedicines reveal how PBOV1 promotes hepatocellular carcinoma for effective gene therapy

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NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-05764-7

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资金

  1. National Natural Science Foundation of China [81671805, U1401242, 81602723, 81502660, 81302550]
  2. National Basic Research Program of China [2015CB755500]
  3. Tianjin Municipal Science and Technology Commission [16JCQNJC10000]
  4. Science and Technology Project of Guangdong Province [2016A020215214, 2017A020215125]
  5. Special Support Program of Guangdong Province
  6. Science and technology innovation youth talent support program [201627015]
  7. Pearl River Science and Technology New Talent of Guangzhou City [201806010076]
  8. Natural Science Foundation of Guangdong Province [S2012020011070]
  9. Postdoctoral Science Foundation of China [2013M530382]
  10. Guangdong Medical Research Foundation [A2015130]
  11. AGILE-KeLin New Talent Program of The First Affiliated Hospital of Sun Yat-sen University

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There exists an urgent medical demand at present to develop therapeutic strategies which can improve the treatment outcome of hepatocellular carcinoma (HCC). Here, we explore the biological functions and clinical significance of PBOV1 in HCC in order to push forward the diagnosis and treatment of HCC. Using theranostical nanomedicines, PBOV1 is verified to be a key oncogene which greatly promotes HCC proliferation, epithelial-to-mesenchymal transition, and stemness by activating the Wnt/beta-catenin signaling pathway. Therefore, single-chain antibody for epidermal growth factor receptor (scAb-EGFR)-targeted nanomedicine effectively silencing the PBOV1 gene exhibits potent anticancer effects. In vivo HCC-targeting siRNA delivery mediated by the theranostical nanomedicine remarkably inhibits the tumor growth and metastasis. In addition, the superparamagnetic iron oxide nanocrystals (SPION)-encapsulated nanomedicines possess high MRI detection sensitivity, which endows them with the potential for MRI diagnosis of HCC. This study shows that PBOV1 represents a prognostic biomarker and therapeutic target for HCC.

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