Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450000, China.
Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450000, China.
Life Sci. 2019 Sep 1;232:116648. doi: 10.1016/j.lfs.2019.116648. Epub 2019 Jul 10.
Laminin γ2 (LAMC2) is over-expressed in ovarian cancer, and its high expression facilitates cell invasion. Nevertheless, the effects of LAMC2 on other ovarian cancer cell functions and its underlying mechanism remain largely unclear. Bioinformatics analysis shows that LAMC2 is a predicted target of miR-125a-5p and miR-193a-3p. Therefore, the present study aimed to investigate the effects of LAMC2 in ovarian cancer progression and determine whether LAMC2 expression is under the regulation of miR-125a-5p or miR-193a-3p in ovarian cancer.
Immunohistochemistry staining, western blot and qPCR were used to detect LAMC2 expression profiles. CCK-8, flow cytometry and tumour formation assays were used to assess cell proliferation, apoptosis and tumorigenesis. The interaction between miR-125a-5p/miR-193a-3p and LAMC2 were determined by the luciferase gene reporter assay.
The results showed that LAMC2 was over-expressed in ovarian cancer tissues and cell lines. Over-expression of LAMC2 significantly promoted cell proliferation and repressed cell apoptosis, as well as increased the expression levels of p38, p-p38, c-myc and CREB, and translocated p38 protein to the nucleus. In addition, the promotion of cell proliferation and repression of cell apoptosis mediated by LAMC2 over-expression were all weakened when p38 was downregulated. Moreover, LAMC2 expression was negatively regulated by miR-125a-5p, which inhibited the nuclear accumulation of p38 protein. Upregulation of LAMC2 significantly abolished the effects of miR-125a-5p on cell proliferation inhibition and cell apoptosis promotion, as well as tumourigenesis repression.
The present study clarified that LAMC2 functioned as an oncogene in ovarian cancer through upregulating p38 under the regulation of miR-125a-5p.
层粘连蛋白γ2（LAMC2）在卵巢癌中过表达，其高表达促进细胞侵袭。然而，LAMC2 对其他卵巢癌细胞功能的影响及其潜在机制在很大程度上仍不清楚。生物信息学分析表明，LAMC2 是 miR-125a-5p 和 miR-193a-3p 的预测靶标。因此，本研究旨在探讨 LAMC2 在卵巢癌进展中的作用，并确定 LAMC2 的表达是否受 miR-125a-5p 或 miR-193a-3p 在卵巢癌中的调控。
免疫组织化学染色、western blot 和 qPCR 用于检测 LAMC2 表达谱。CCK-8、流式细胞术和肿瘤形成实验用于评估细胞增殖、凋亡和肿瘤发生。通过荧光素酶基因报告基因检测确定 miR-125a-5p/miR-193a-3p 与 LAMC2 之间的相互作用。
结果表明，LAMC2 在卵巢癌组织和细胞系中过度表达。LAMC2 的过表达显著促进细胞增殖，抑制细胞凋亡，并增加 p38、p-p38、c-myc 和 CREB 的表达水平，并将 p38 蛋白转位到细胞核。此外，当下调 p38 时，LAMC2 过表达介导的细胞增殖促进和细胞凋亡抑制作用均减弱。此外，LAMC2 的表达受 miR-125a-5p 的负调控，抑制 p38 蛋白的核积累。上调 LAMC2 显著消除了 miR-125a-5p 对细胞增殖抑制和细胞凋亡促进以及肿瘤发生抑制的作用。
本研究阐明了在 miR-125a-5p 的调控下，LAMC2 通过上调 p38 在卵巢癌中作为癌基因发挥作用。
