Department of Gynecology and Obstetrics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China.
Center for Reproductive Medicine and Center for Prenatal Diagnosis, the First Hospital, Jilin University,71 Xinmin Street,Changchun, Jilin Province 130021, PR China.
Biomed Pharmacother. 2018 Oct;106:61-67. doi: 10.1016/j.biopha.2018.06.112. Epub 2018 Jun 26.
The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), was reportedly to be highly expressed in a variety of tumors including ovarian cancer (OC). However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of OC remains largely unknown. PVT1 and miR-133a expression were detected by quantitative real time PCR(qRT-PCR) assays in OC tissues and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometer, wound healing and transwell invasion assays were performed to evaluate cell proliferation, cycle, migration and invasion abilities, respectively. qRT-PCR and luciferase reporter assays demonstrated PVT1 regulated miR-133a expression. Here, we discovered that PVT1 shows higher expression in OC tissues than in normal ovarian tissues, and patients who show higher expression of PVT1 have worse progression-free and overall survivals compared to lower expression of PVT1. Additionally, we observed that knockdown of PVT1 significantly inhibited OC cell proliferation, and decreased the migration and invasion capabilities of OC cells. Mechanistically, miR-133a was identified to serve as a direct downstream target of PVT1 in OC. Knockdown of PVT1 inhibited cell proliferation, migration and invasion through negative regulating miR-133a in OC cells. Taken together, our finding shows that PVT1 may be a novel biomarker for prognosis and a promising therapeutic target for OC.
长链非编码 RNA 浆细胞瘤变异易位基因 1(PVT1)在多种肿瘤中高表达,包括卵巢癌(OC)。然而,PVT1 在 OC 发生和进展中的作用和作用机制在很大程度上仍然未知。通过定量实时 PCR(qRT-PCR)检测 OC 组织和细胞系中 PVT1 和 miR-133a 的表达。通过细胞计数试剂盒-8(CCK-8)、流式细胞仪、划痕愈合和 Transwell 侵袭实验分别评估细胞增殖、周期、迁移和侵袭能力。qRT-PCR 和荧光素酶报告基因实验表明 PVT1 调节 miR-133a 的表达。在这里,我们发现 PVT1 在 OC 组织中的表达高于正常卵巢组织,并且 PVT1 表达较高的患者与 PVT1 表达较低的患者相比,无进展生存期和总生存期更差。此外,我们观察到敲低 PVT1 可显著抑制 OC 细胞增殖,并降低 OC 细胞的迁移和侵袭能力。在机制上,miR-133a 被鉴定为 OC 中 PVT1 的直接下游靶标。敲低 PVT1 通过负调控 OC 细胞中的 miR-133a 抑制细胞增殖、迁移和侵袭。总之,我们的研究结果表明,PVT1 可能是 OC 预后的新型生物标志物和有前途的治疗靶点。