Li Min, Chi Chi, Zhou Liqin, Chen Youguo, Tang Xiuwu
Department of Gynecology & Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Department of Gynecology & Obstetrics, Suzhou Xiangcheng People's Hospital, Suzhou 215006, Jiangsu Province, China.
J Cancer. 2021 Jan 1;12(2):611-621. doi: 10.7150/jca.52234. eCollection 2021.
Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is a dysregulated gene in malignancy and is associated with oncogenesis. In this study, we found PVT1 RNA was an ovarian specific expressing gene, and overexpressed in multiple cancer types, including ovarian cancer (OV). Higher expression levels of PVT1 are related to shorter survival time in OV patients, especially in patients with advanced stage and grade. Recent studies indicated circular PVT1 also had an important role in cancer progression, whose roles in OV remain unclear. Knockdown of circular PVT1 significantly suppressed OV cell proliferation, migration and invasion. Bioinformatics analysis demonstrated that circular PVT1 was involved in regulating angiogenesis, osteoblast differentiation, regulation of cell growth, type B pancreatic cell proliferation, negative regulation of apoptotic process, phospholipid homeostasis, regulation of neurogenesis, definitive hemopoiesis, cell migration, regulation of glucose metabolic process, central nervous system development and type 2 immune response. Our data showed miR-149-5p targeted FOXM1, which was regulated by circular PVT1. Forkhead Box M1 (FOXM1) expression in ovarian cancer exhibited high level when compared with normal tissues, and had relation with relatively poor survival. FOXM1 promoted cell viability and reduced FOXM1 could rescue circular influence of circular PVT1-caused carcinoma induction. In conclusion, circular PVT1 increased FOXM1 level via binding to miR-149-5p and thus affected ovarian cancer cell viability and migration.
长链非编码RNA浆细胞瘤变异易位1(PVT1)是一种在恶性肿瘤中失调的基因,与肿瘤发生相关。在本研究中,我们发现PVT1 RNA是一种卵巢特异性表达基因,在多种癌症类型中过表达,包括卵巢癌(OV)。PVT1的高表达水平与OV患者较短的生存时间相关,尤其是晚期和高分级患者。最近的研究表明,环状PVT1在癌症进展中也起重要作用,但其在OV中的作用仍不清楚。敲低环状PVT1可显著抑制OV细胞的增殖、迁移和侵袭。生物信息学分析表明,环状PVT1参与调节血管生成、成骨细胞分化、细胞生长调节、B型胰腺细胞增殖、凋亡过程的负调节、磷脂稳态、神经发生调节、确定性造血、细胞迁移、葡萄糖代谢过程调节、中枢神经系统发育和2型免疫反应。我们的数据显示,miR-149-5p靶向受环状PVT1调控的FOXM1。与正常组织相比,卵巢癌中叉头框M1(FOXM1)表达水平较高,且与相对较差的生存率相关。FOXM1促进细胞活力,降低FOXM1可挽救环状PVT1诱导癌变的环状影响。总之,环状PVT1通过与miR-149-5p结合增加FOXM1水平,从而影响卵巢癌细胞的活力和迁移。