Nanomedicines reveal how PBOV1 promotes hepatocellular carcinoma for effective gene therapy.

Nanomedicines reveal how PBOV1 promotes hepatocellular carcinoma for effective gene therapy.
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纳米药物揭示了 PBOV1 如何促进肝细胞癌的有效基因治疗。

DOI:
10.1038/s41467-018-05764-7
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发表时间:
2018-08-24
影响因子:
16.6
通讯作者:
Shuai X
Shuai X
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Guo Y;Wu Z;Shen S;Guo R;Wang J;Wang W;Zhao K;Kuang M;Shuai X

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目前迫切需要制定改善肝细胞癌治疗效果的治疗策略。本文探讨PBOV1在HCC中的生物学功能及临床意义,以期推动HCC的诊断和治疗。利用纳米治疗药物,PBOV1被证实是一个关键的癌基因,通过激活Wnt/β-catenin信号通路,极大地促进了HCC的增殖、上皮细胞向间质细胞的转化和干细胞的形成。因此,表皮生长因子受体(sca - egfr)靶向纳米药物单链抗体能有效地沉默PBOV1基因,显示出强大的抗癌作用。治疗性纳米药物介导的体内hcc靶向siRNA递送可显著抑制肿瘤的生长和转移。此外,超顺磁性氧化铁纳米晶体(SPION)包封的纳米药物具有较高的MRI检测灵敏度,这使其具有MRI诊断HCC的潜力。本研究表明PBOV1是HCC的预后生物标志物和治疗靶点。
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/β-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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