Department of Gynecology, Maternity and Child Health Care Hospital of Hubei Province.
Department of Obstetrics and Gynecology, School of Medicine, Wuhan University of Science and Technology, Wuhan.
Anticancer Drugs. 2022 Sep 1;33(8):701-709. doi: 10.1097/CAD.0000000000001314. Epub 2022 Aug 10.
An increasing number of studies have confirmed that microRNAs (miRNAs) are involved in various biological processes, including tumor growth and drug resistance. MiR-4284 has been proved to be abnormally regulated in several cancers, but the function of miR-4284 in ovarian carcinoma (OC) is unclear. Paclitaxel resistance is a key obstacle in OC treatment. Here, the role of miR-4284 in cell sensitivity to paclitaxel in OC was investigated. Two OC cell lines (SKOV3ip1 and HeyA8) were utilized for the establishment of paclitaxel-resistant cell lines. Reverse transcription-quantitative PCR (RT-qPCR) was applied to analyze the levels of miR-4284 and potential mRNAs in OC cell lines. Western blotting was performed to evaluate the levels of DNA meiotic recombinase 1 (DMC1) protein and cell cycle-associated proteins. Identification of the relationship between miR-4284 and DMC1 was achieved by luciferase reporter assay. CCK-8 and flow cytometry assays were utilized for evaluating the impact of miR-4284 on the malignant characteristics of paclitaxel-resistant OC cells. MiR-4284 was upregulated in paclitaxel-resistant OC cell lines and correlated with an adverse prognosis in OC patients. Depletion of miR-4284 suppressed cell proliferation and cell cycle progression of paclitaxel-resistant OC. MiR-4284 targeted DMC1 which was downregulated in paclitaxel-resistant cells and reversed the inhibitory influence of miR-4284 silencing on the malignant characters of paclitaxel-resistant OC cells. MiR-4284 targets DMC1 to suppress sensitivity to paclitaxel in human OC cells.
越来越多的研究证实，微小 RNA（miRNA）参与多种生物学过程，包括肿瘤生长和耐药性。miR-4284 在几种癌症中被证明存在异常调节，但 miR-4284 在卵巢癌（OC）中的功能尚不清楚。紫杉醇耐药是 OC 治疗的关键障碍。本研究旨在探讨 miR-4284 在 OC 细胞对紫杉醇敏感性中的作用。利用两种 OC 细胞系（SKOV3ip1 和 HeyA8）建立紫杉醇耐药细胞系。采用逆转录定量 PCR（RT-qPCR）分析 OC 细胞系中 miR-4284 和潜在 mRNA 的水平。采用 Western blot 检测 DNA 减数分裂重组酶 1（DMC1）蛋白和细胞周期相关蛋白的水平。通过荧光素酶报告实验鉴定 miR-4284 与 DMC1 之间的关系。CCK-8 和流式细胞术检测 miR-4284 对紫杉醇耐药 OC 细胞恶性特征的影响。miR-4284 在紫杉醇耐药 OC 细胞系中上调，并与 OC 患者的不良预后相关。下调 miR-4284 抑制紫杉醇耐药 OC 细胞的增殖和细胞周期进程。miR-4284 靶向 DMC1，而 DMC1 在紫杉醇耐药细胞中下调，并且 miR-4284 沉默对紫杉醇耐药 OC 细胞恶性特征的抑制作用被逆转。miR-4284 通过靶向 DMC1 抑制人 OC 细胞对紫杉醇的敏感性。
