文章：

上调microRNA-3129通过CD44抑制上皮性卵巢癌

Upregulation of microRNA-3129 suppresses epithelial ovarian cancer through CD44 

原文发布日期：2018-06-19 

英文摘要：

The purpose of this work is to evaluate whether human microRNA-3129 (hsa-miR-3129) may functionally regulate cancer development, possibly through downstream target CD44 in human epithelial ovarian cancer (EOC). Direct targeting of hsa-miR-3129 on human CD44 transcript was evaluated using a dual-luciferase reporter assay. Gene expression of hsa-miR-3129 in immortal EOC cell lines was evaluated by qRT-PCR. Lentivirus-mediated hsa-miR-3129 upregulation or downregulation was conducted in SK-OV-3 and CAOV-3 cells, in which endogenous hsa-miR-3129 and CD44 expressions were then measured. In hsa-miR-3129 upregulated or downregulated EOC cells, functional assays were applied to evaluate EOC proliferation, bufalin chemoresistance in vitro, or xenotransplantation in vivo. Moreover, CD44 was ectopically overexposed in hsa-miR-3129 upregulated EOC cells to functionally evaluate the correlation between hsa-miR-3129 and CD44 in EOC. Dual-luciferase reporter assay confirmed hsa-miR-3129 directly binds CD44. QRT-PCR revealed that hsa-miR-3129 was substantially downregulated in EOC cell lines. In SK-OV-3 and CAOV-3 cells, lentivirus-induced hsa-miR-3129 upregulation downregulated CD44 whereas hsa-miR-3129 downregulation did not affect CD44 expression. Hsa-miR-3129 upregulation had significant anti-cancer effects by inhibiting EOC proliferation, increasing bufalin chemoresistance, and suppressing xenotransplantation. On the other hand, overexpressing CD44 reversed the anti-cancer functions by hsa-miR-3129 upregulation in EOC cells. In conclusion, Has-miR-3129 is a functional regulator, possibly through reverse targeting on CD44, in EOC. 

摘要翻译：

本研究旨在评估人microRNA-3129（hsa-miR-3129）是否可能通过下游靶标CD44调控人类上皮性卵巢癌（EOC）的癌症发展进程。我们采用双荧光素酶报告基因检测法验证hsa-miR-3129对人类CD44转录本的直接靶向作用，通过qRT-PCR技术检测永生化EOC细胞系中hsa-miR-3129的基因表达水平。在SK-OV-3和CAOV-3细胞中通过慢病毒介导技术实现hsa-miR-3129的上调与下调，并检测其内源性hsa-miR-3129与CD44的表达变化。在调控hsa-miR-3129表达的EOC细胞中，通过功能实验评估其对EOC增殖能力、体外蟾毒灵耐药性及体内异种移植瘤生长的影响。此外，在hsa-miR-3129上调的EOC细胞中外源性过表达CD44，以功能学角度验证hsa-miR-3129与CD44在EOC中的调控关系。研究结果显示：双荧光素酶报告基因实验证实hsa-miR-3129可直接结合CD44；qRT-PCR检测表明hsa-miR-3129在EOC细胞系中显著低表达；在SK-OV-3和CAOV-3细胞中，慢病毒诱导的hsa-miR-3129上调会降低CD44表达，而其下调则不影响CD44表达；hsa-miR-3129上调通过抑制EOC细胞增殖、增强蟾毒灵耐药性及抑制异种移植瘤生长发挥显著抗癌作用；而CD44的过表达可逆转hsa-miR-3129上调在EOC细胞中产生的抗癌功能。综上所述，hsa-miR-3129可能通过反向靶向调控CD44成为EOC中的功能性调节因子。

原文链接：

Upregulation of microRNA-3129 suppresses epithelial ovarian cancer through CD44