Department of Gynecology and Oncology, Xinxiang Central Hospital, Xinxiang, Henan, 453000, China.
Obstetrics&Gynecology Department, Zhongnan Hospital of Wuhan University, Wuchang District, Wuhan City, Hubei, 430070, China.
Biomed Pharmacother. 2018 Nov;107:712-720. doi: 10.1016/j.biopha.2018.08.044. Epub 2018 Aug 20.
MicroRNAs have been demonstrated to play a crucial role in the development of ovarian cancer. Many studies prove that forms of miR-135a, including miR-135a-5p and miR-135a-3p, serve as tumour suppressors in multiple cancers. Nevertheless, the precise function of miR-135a-3p and the molecular mechanisms underlying the involvement of miR-135a-3p in ovarian carcinoma cell growth and metastasis remain largely unknown. Herein, we report that miR-135a-3p expression was significantly downregulated in ovarian carcinoma tissues compared with corresponding adjacent non-tumour tissues. Ectopic miR-135a-3p expression inhibited ovarian carcinoma cell proliferation, migration and invasion in vitro. Additionally, the overexpression of miR-135a-3p inhibited epithelial-mesenchymal transition (EMT) in ovarian cancer cells. A luciferase reporter assay confirmed that the C-C chemokine receptor type 2 (CCR2) gene was the target of miR-135a-3p. In addition, CCR2 depletion mimicked the inhibitory effects of miR-135a-3p on ovarian cancer cells in vitro. Rescue experiments using CCR2 overexpression further verified that CCR2 was a functional target of miR-135a-3p. Xenograft model assays demonstrated that miR-135a-3p functions as an anti-oncogene by targeting CCR2 in vivo. Taken together, these data prove that miR-135a-3p serves as a tumour suppressor gene in ovarian cancer by regulating CCR2.
MicroRNAs 已被证明在卵巢癌的发展中发挥着关键作用。许多研究证明,miR-135a 的多种形式,包括 miR-135a-5p 和 miR-135a-3p,在多种癌症中作为肿瘤抑制因子发挥作用。然而,miR-135a-3p 的精确功能以及 miR-135a-3p 参与卵巢癌细胞生长和转移的分子机制在很大程度上仍然未知。在此,我们报告 miR-135a-3p 在卵巢癌组织中的表达明显低于相应的相邻非肿瘤组织。外源性 miR-135a-3p 表达抑制卵巢癌细胞在体外的增殖、迁移和侵袭。此外,miR-135a-3p 的过表达抑制了卵巢癌细胞中的上皮-间充质转化(EMT)。荧光素酶报告基因实验证实 C-C 趋化因子受体 2(CCR2)基因是 miR-135a-3p 的靶基因。此外,CCR2 耗竭模拟了 miR-135a-3p 在体外对卵巢癌细胞的抑制作用。使用 CCR2 过表达进行的挽救实验进一步验证了 CCR2 是 miR-135a-3p 的功能性靶基因。异种移植模型实验表明,miR-135a-3p 通过靶向 CCR2 在体内发挥抑癌基因的作用。总之,这些数据证明 miR-135a-3p 通过调节 CCR2 作为肿瘤抑制基因在卵巢癌中发挥作用。