Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion.
Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion.
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DOI：
10.1007/s11095-013-1219-9
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发表时间：
2015-03
影响因子：
3.7
通讯作者：
Yue, Junming
中科院分区：
文献类型：
--
作者：
Guo, Yuqi;Tian, Peng;Yang, Chuanhe;Liang, Zhibing;Li, Min;Sims, Michelle;Lu, Lu;Zhang, Zhan;Li, Hongwei;Pfeffer, Lawrence M.;Yue, Junming
目的探讨卵巢癌中miRNA生物合成途径的关键组分DiGeorge关键区8（DGCR 8）的作用。免疫组化检测DGCR 8在卵巢癌细胞中的表达，并利用慢病毒shRNA实现DGCR 8在卵巢癌细胞中的敲低。使用Nanostring miRNA阵列确定miRNA的差异表达，并通过实时RT-PCR验证。DGCR 8在卵巢癌组织中呈高表达。DGCR 8表达的敲低抑制细胞增殖、迁移和侵袭，以及使细胞对化疗药物顺铂诱导的细胞凋亡敏感。DGCR 8基因敲减细胞的细胞存活途径包括ERK 1/2丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶/AKT减弱。DGCR 8敲低导致miRNA基因表达失调。miR-27 b被鉴定为DGCR 8敲减细胞中下调最高的miRNA，并促进卵巢癌细胞的细胞增殖。DGCR 8在卵巢癌中作为癌基因发挥作用，其部分由miR-27 b介导。
To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer. The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR. DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown resulting in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells. DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.
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