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DPEP1 是 miR-193a-5p 的直接靶标，并通过 PI3K/Akt/mTOR 通路促进肝癌的进展。

DPEP1 is a direct target of miR-193a-5p and promotes hepatoblastoma progression by PI3K/Akt/mTOR pathway.

机构信息

Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

出版信息

Cell Death Dis. 2019 Sep 20;10(10):701. doi: 10.1038/s41419-019-1943-0.

DOI:10.1038/s41419-019-1943-0
PMID:31541079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6754441/
Abstract

Hepatoblastoma (HB) is the most common hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Increasing evidence shows that dipeptidase 1 (DPEP1) has pivotal function in tumorigenesis in multiple tumors. However, the expression pattern, biological function, and underlying mechanism of DPEP1 in HB have not been reported. Here we showed that DPEP1 was significantly upregulated and was associated with poor prognosis in HB patients. In vitro and in vivo assays indicated that silencing DPEP1 significantly suppressed HB cell proliferation, migration, and invasion, while DPEP1 overexpression exhibited the opposite effect. In addition, we identified that DPEP1 was a direct target of microRNA-193a-5p (miR-193a-5p). Functional experiments demonstrated that overexpression of miR-193a-5p significantly inhibited cell proliferation and invasion of HB cells, while the inhibitory effect could be reversed by DPEP1 overexpression. Moreover, miR-193a-5p was decreased in HB tumor tissues and associated with a poor clinical prognosis. Mechanistically, our results indicated that the miR-193a-5p/DPEP1 axis participated to the progression of HB via regulating the PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin) signaling. In conclusion, our findings suggest that the miR-193a-5p /DPEP1 axis might be a good prognostic predictor and therapeutic target in HB.

摘要

肝细胞瘤 (HB) 是儿童期最常见的肝肿瘤，由于其复发和转移，治疗效果仍不理想。越来越多的证据表明二肽酶 1 (DPEP1) 在多种肿瘤的肿瘤发生中具有关键作用。然而，DPEP1 在 HB 中的表达模式、生物学功能和潜在机制尚未报道。在这里，我们发现 DPEP1 在 HB 患者中显著上调，并与预后不良相关。体外和体内实验表明，沉默 DPEP1 显著抑制 HB 细胞的增殖、迁移和侵袭，而 DPEP1 的过表达则表现出相反的效果。此外，我们确定 DPEP1 是 microRNA-193a-5p (miR-193a-5p) 的直接靶标。功能实验表明，miR-193a-5p 的过表达显著抑制 HB 细胞的增殖和侵袭，而 DPEP1 的过表达可以逆转这种抑制作用。此外，miR-193a-5p 在 HB 肿瘤组织中减少，并与不良的临床预后相关。机制上，我们的结果表明，miR-193a-5p/DPEP1 轴通过调节 PI3K/Akt/mTOR (磷脂酰肌醇-3-激酶/Akt/雷帕霉素的哺乳动物靶标) 信号通路参与 HB 的进展。总之，我们的研究结果表明，miR-193a-5p/DPEP1 轴可能是 HB 的一个良好的预后预测因子和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/aba8e382121c/41419_2019_1943_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/d6818d8fbbe2/41419_2019_1943_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/68643aee6a5d/41419_2019_1943_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/8fd3a9fed4a6/41419_2019_1943_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/aaf20c02e7cb/41419_2019_1943_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/fe38288f2c33/41419_2019_1943_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/dab43b01888b/41419_2019_1943_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/6f3149625d0c/41419_2019_1943_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/aba8e382121c/41419_2019_1943_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/d6818d8fbbe2/41419_2019_1943_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/68643aee6a5d/41419_2019_1943_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/8fd3a9fed4a6/41419_2019_1943_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/aaf20c02e7cb/41419_2019_1943_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/fe38288f2c33/41419_2019_1943_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/dab43b01888b/41419_2019_1943_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/6f3149625d0c/41419_2019_1943_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f6/6754441/aba8e382121c/41419_2019_1943_Fig8_HTML.jpg

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