Ovarian cancer is one the prevalent cancers in women and is responsible for 5% of all the cancer related mortalities in women. Owing to late diagnosis, frequent relapses, side effects of chemotherapy, development of drug resistance, there is pressing need to screen out novel and effective treatment options. Accumulating evidences suggest that miRNAs may prove essential therapeutic targets for the treatment of cancer. This study was designed to investigate the role and therapeutic potential of miR-34 in ovarian cancer. It was found that miR-34 is significantly downregulated in ovarian cancer cell lines. Overexpression of miR-34 causes significant decrease in the proliferation of OVACAR-3 ovarian cancer cells via activation of apoptosis and autophagy. The miR-34 overexpression was concomitant with upsurge of apoptosis related proteins (Bax) and the autophagy associated protein (LC3 II and p62). TargetScan analysis showed Notch 1 to be the main target of miR-34 in OVACAR-3 cells which was further validated by luciferase reporter assay. The qRT-PCR results showed Notch 1 to be 3.2–4.1 fold higher in the ovarian cancer cell lines relative to the non-cancerous cells. Nonetheless, miR-34 overexpression in OVACAR-3 cells resulted in the post-transcriptional suppression of Notch 1 expression. Silencing of Notch 1 also caused inhibition of OVACAR-3 cell proliferation via induction of apoptosis and autophagy. Overexpression of Notch 1 could partially rescue the effects of miR-34 overexpression on the proliferation of OVACAR-3 cells. Moreover, overexpression of miR-34 causes significant inhibition of the invasion of the OVACAR-3 cells. The findings of the present study indicate the tumor suppressive role of miR-34 in ovarian cancer and may therefore prove to be a potential therapeutic target.

卵巢癌是女性常见的癌症之一，占女性所有癌症相关死亡率的 5%。由于诊断晚、复发频繁、化疗副作用大、耐药性的产生，迫切需要筛选新颖有效的治疗方案。越来越多的证据表明 miRNA 可能成为治疗癌症的重要治疗靶点。本研究旨在探讨 miR-34 在卵巢癌中的作用和治疗潜力。研究发现，miR-34在卵巢癌细胞系中显着下调。 miR-34 的过度表达通过激活细胞凋亡和自噬导致 OVACAR-3 卵巢癌细胞的增殖显着减少。 miR-34 过表达伴随着凋亡相关蛋白 (Bax) 和自噬相关蛋白 (LC3 II 和 p62) 的激增。 TargetScan 分析显示 Notch 1 是 OVACAR-3 细胞中 miR-34 的主要靶标，这一点通过荧光素酶报告基因检测进一步验证。 qRT-PCR 结果显示，卵巢癌细胞系中的 Notch 1 比非癌细胞高 3.2-4.1 倍。尽管如此，OVACAR-3 细胞中 miR-34 的过表达导致了 Notch 1 表达的转录后抑制。 Notch 1 的沉默还通过诱导细胞凋亡和自噬抑制 OVACAR-3 细胞增殖。 Notch 1 的过表达可以部分挽救 miR-34 过表达对 OVACAR-3 细胞增殖的影响。此外，miR-34的过度表达会显着抑制OVACAR-3细胞的侵袭。 本研究的结果表明 miR-34 在卵巢癌中具有肿瘤抑制作用，因此可能被证明是一个潜在的治疗靶点。