Department of Obstetrics and Gynecology, The Third People's Hospital of Jinan, Jinan, Shandong 250132, China.
Department of Cardiology, The Third People's Hospital of Jinan, Jinan, Shandong 250132, China.
Arch Biochem Biophys. 2018 Aug 1;651:21-27. doi: 10.1016/j.abb.2018.05.007. Epub 2018 May 31.
Ovarian cancer is among the most prevalent and lethal types of cancers in women. Several factors such as late diagnosis, unavailability of the reliable biomarkers, frequent relapses and dearth of efficient therapeutic targets form bottleneck in the treatment of ovarian cancers. In this study we investigated the potential of less studied miR-299-3p as the therapeutic target for the treatment of ovarian cancer. The results of the present investigation revealed that miR-299 is significantly upregulated in the ovarian cancers and suppression of its expression inhibits the proliferation by induction of apoptosis as well suppresses migration and invasion of the SKOV3 cancers cells. Further, OCT-4 was found to be putative target of miR-99-3p in ovarian cancer and inhibition of OCT-4 had similar effects as that of miR-299 inhibition on cell migration and invasion. Intriguingly, even overexpression of miR-299-3p could not rescue the effects of OCT-4 suppression on SKOV3 cell proliferation, migration and invasion. On contrary, overexpression of OCT-4 in SKOV3 cells transfected with miR-299-3p transfected could nullify the effects of miR-200-3p on proliferation, migration and invasion of the SKOV3 cells. Taken together, miR-299-3p regulated cell proliferation and metastasis by modulating the expression of OCT-4 and as such may prove to be an important therapeutic target.
卵巢癌是女性中最常见和最致命的癌症之一。晚期诊断、缺乏可靠的生物标志物、频繁复发以及缺乏有效的治疗靶点等因素,成为卵巢癌治疗的瓶颈。在这项研究中,我们研究了研究较少的 miR-299-3p 作为治疗卵巢癌的治疗靶点的潜力。本研究结果表明,miR-299 在卵巢癌中显著上调,抑制其表达通过诱导细胞凋亡抑制增殖,并抑制 SKOV3 癌细胞的迁移和侵袭。此外,OCT-4 被发现是卵巢癌中 miR-99-3p 的假定靶标,抑制 OCT-4 的作用与 miR-299 抑制对细胞迁移和侵袭的作用相似。有趣的是,即使过表达 miR-299-3p 也不能挽救 OCT-4 抑制对 SKOV3 细胞增殖、迁移和侵袭的影响。相反,在转染 miR-299-3p 的 SKOV3 细胞中转染 OCT-4 的过表达可以消除 miR-200-3p 对 SKOV3 细胞增殖、迁移和侵袭的影响。综上所述,miR-299-3p 通过调节 OCT-4 的表达来调节细胞增殖和转移,因此可能成为一个重要的治疗靶点。