Department of Gynecology and Obstetrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, China.
Department of Rheumatology, The Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, China.
Biomed Pharmacother. 2019 Jan;109:595-601. doi: 10.1016/j.biopha.2018.10.148. Epub 2018 Nov 3.
MicroRNAs are small non-coding RNAs which play important roles in tumor progression. MiR-383-5p has been characterized as a cancer suppressor in several cancers. The aim of theses present study was to explore the role of miR-383-5p in the proliferation and chemosensitivity of ovarian cancer cells. MiR-383-5p expression was down-regulated while the expression of TRIM27 was up-regulated in ovarian cancer tissues and cell lines. We came up with the hypothesis that miR-383-5p might be involved in the tumor progression and chemoresistance of ovarian cancer through targeting TRIM27. Bioinformatics study and Luciferase reporter assay indicated that TRIM27 was a target of miR-383-5p and negatively regulated by miR-383-5p in ovarian cancer cells. Up-regulation of miR-383-5p was found to suppress cell proliferation and decrease Ki67 and PCNA expression in ovarian cancer cells (OVCAR3, A2780), suggesting that overexpressed miR-383-5p inhibited cell proliferation of ovarian cancer cells. In addition, up-regulation of miR-383-5p decreased the IC value of ovarian cancer cells to paclitaxel and increased cell apoptosis rate under the treatment of paclitaxel, indicating that overexpressed miR-383-5p enhanced chemosensitivity in ovarian cancer cells. However, overexpressed TRIM27 by pcDNA3.1-TRIM27 transfection counteracted the inhibitory effect of miR-383-5p on cell proliferation and chemoresistance in ovarian cancer cells. In vivo experiments also revealed that tumor growth could be inhibited by miR-383-5p mimic. Taken together, this present study found that miR-383-5p was lowly expressed while TRIM27 was highly expressed in ovarian cancer. Up-regulation of miR-383-5p inhibited cell proliferation, tumor growth and enhanced chemosensitivity of ovarian cancer cells through suppressing TRIM27 expression. Therefore, miR-383-5p/TRIM27 axis may be the potential target for the treatment of ovarian cancer.
微小 RNA 是一类在肿瘤进展中发挥重要作用的非编码小 RNA。miR-383-5p 在几种癌症中被鉴定为一种肿瘤抑制因子。本研究旨在探讨 miR-383-5p 在卵巢癌细胞增殖和化疗敏感性中的作用。miR-383-5p 在卵巢癌组织和细胞系中的表达下调,而 TRIM27 的表达上调。我们假设 miR-383-5p 可能通过靶向 TRIM27 参与卵巢癌的肿瘤进展和化疗耐药。生物信息学研究和荧光素酶报告基因实验表明,TRIM27 是 miR-383-5p 的靶基因,并在卵巢癌细胞中受 miR-383-5p 的负调控。上调 miR-383-5p 可抑制卵巢癌细胞(OVCAR3、A2780)的增殖,并降低 Ki67 和 PCNA 的表达,表明过表达的 miR-383-5p 抑制卵巢癌细胞的增殖。此外,上调 miR-383-5p 降低了卵巢癌细胞对紫杉醇的 IC 值,并增加了紫杉醇处理后的细胞凋亡率,表明过表达的 miR-383-5p 增强了卵巢癌细胞的化疗敏感性。然而,pcDNA3.1-TRIM27 转染过表达 TRIM27 可拮抗 miR-383-5p 对卵巢癌细胞增殖和化疗耐药性的抑制作用。体内实验也表明 miR-383-5p 模拟物可抑制肿瘤生长。综上所述,本研究发现 miR-383-5p 在卵巢癌中低表达,而 TRIM27 高表达。上调 miR-383-5p 通过抑制 TRIM27 的表达抑制卵巢癌细胞的增殖、肿瘤生长和增强化疗敏感性。因此,miR-383-5p/TRIM27 轴可能是治疗卵巢癌的潜在靶点。