Gao Jianfen, Liu Faqin, Zhao Xia, Zhang Ping
Department of Gynecology, People's Hospital of Zhangqiu District, Jinan, Shandong 250200, P.R. China.
Operating Room, People's Hospital of Zhangqiu District, Jinan, Shandong 250200, P.R. China.
Exp Ther Med. 2021 Apr;21(4):307. doi: 10.3892/etm.2021.9738. Epub 2021 Feb 1.
The aim of the present study was to determine the role of long non-coding RNA (lncRNA) forkhead box D2 antisense 1 (FOXD2-AS1) in the development of ovarian cancer, investigate the underlying mechanisms and provide a potential diagnostic biomarker for ovarian cancer. A total of 39 ovarian cancer patients were included, and the ovarian cancer tissues and paracancer tissues were obtained. The ovarian cancer cell lines SKOV3 and OVCAR3 and the human ovarian normal epithelial cell line IOSE80 were cultured. The expression of lncRNA FOXD2-AS1 and miR-4492 was detected by reverse transcription-quantitative PCR. Small interfering RNA targeting FOXD2-AS1 (si-FOXD2-AS1), microRNA (miR)-4492 mimics, miR-4492 inhibitor and their corresponding controls were transfected into cells. The proliferation was detected with a Cell-Couting-Kit-8 assay, and migration and invasion were determined using Transwell assays. The mutual binding site of lncRNA FOXD2-AS1 and miR-4492 was predicted with the miRDB database and verified by a luciferase reporter assay. Finally, a rescue assay was performed. The results suggested that lncRNA FOXD2-AS1 was upregulated in ovarian cancer tissues and cell lines. si-FOXD2-AS1 was able to inhibit the proliferation, migration and invasion of ovarian cancer cells. lncRNA FOXD2-AS1 was confirmed to directly target miR-4492. The expression of lncRNA FOXD2-AS1 and miR-4492 exhibited a negative correlation. In a rescue experiment, miR-4492 inhibitor abrogated the effect of siFOXD2-AS1 in SKOV3 and OVCAR3 cell lines. In conclusion, lncRNA FOXD2-AS1 promotes the proliferation and invasion of ovarian cancer cells via regulating the expression of miR-4492. It may be a novel potential diagnostic biomarker and therapeutic target for ovarian cancer.
本研究的目的是确定长链非编码RNA(lncRNA)叉头框D2反义1(FOXD2-AS1)在卵巢癌发生发展中的作用,探究其潜在机制,并为卵巢癌提供一种潜在的诊断生物标志物。共纳入39例卵巢癌患者,获取其癌组织及癌旁组织。培养卵巢癌细胞系SKOV3和OVCAR3以及人卵巢正常上皮细胞系IOSE80。采用逆转录定量聚合酶链反应检测lncRNA FOXD2-AS1和miR-4492的表达。将靶向FOXD2-AS1的小干扰RNA(si-FOXD2-AS1)、微小RNA(miR)-4492模拟物、miR-4492抑制剂及其相应对照转染至细胞中。采用细胞计数试剂盒-8法检测细胞增殖情况,采用Transwell法检测细胞迁移和侵袭能力。利用miRDB数据库预测lncRNA FOXD2-AS1与miR-4492的相互结合位点,并通过荧光素酶报告基因检测进行验证。最后进行了挽救实验。结果表明,lncRNA FOXD2-AS1在卵巢癌组织和细胞系中表达上调。si-FOXD2-AS1能够抑制卵巢癌细胞的增殖、迁移和侵袭。证实lncRNA FOXD2-AS1直接靶向miR-4492。lncRNA FOXD2-AS1与miR-4492的表达呈负相关。在挽救实验中,miR-4492抑制剂消除了siFOXD2-AS1对SKOV3和OVCAR3细胞系的作用。综上所述,lncRNA FOXD2-AS1通过调控miR-4492的表达促进卵巢癌细胞的增殖和侵袭。它可能是卵巢癌一种新的潜在诊断生物标志物和治疗靶点。
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