沉默双链RNA结合蛋白DGCR8可抑制卵巢癌细胞的增殖、迁移和侵袭。

Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion.

作者信息

Guo Yuqi, Tian Peng, Yang Chuanhe, Liang Zhibing, Li Min, Sims Michelle, Lu Lu, Zhang Zhan, Li Hongwei, Pfeffer Lawrence M, Yue Junming

出版信息

Pharm Res. 2015 Mar;32(3):769-78. doi: 10.1007/s11095-013-1219-9.

PURPOSE

To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer.

METHODS

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.

RESULTS

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 results 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.

CONCLUSIONS

DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.

目的

评估微小RNA生物合成途径的关键组成部分——狄乔治关键区域8（DGCR8）在卵巢癌中的作用。

方法

通过免疫染色检测DGCR8在卵巢癌中的表达，并使用慢病毒短发夹RNA（shRNA）实现卵巢癌细胞中DGCR8的敲低。使用纳米串微小RNA芯片确定微小RNA的差异表达，并通过实时逆转录聚合酶链反应（RT-PCR）进行验证。

结果

DGCR8在卵巢癌中高表达。敲低DGCR8表达可抑制细胞增殖、迁移和侵袭，并使细胞对化疗药物顺铂诱导的凋亡敏感。在敲低DGCR8的细胞中，包括细胞外信号调节激酶1/2（ERK1/2）丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）在内的细胞存活途径减弱。敲低DGCR8导致微小RNA基因表达失调。miR-27b被确定为敲低DGCR8的细胞中下调最明显的微小RNA，并促进卵巢癌细胞的增殖。