J Cancer 2021; 12(2):611-621. doi:10.7150/jca.52234

Research Paper

Circular PVT1 regulates cell proliferation and invasion via miR-149-5p/FOXM1 axis in ovarian cancer

Min Li1#, Chi Chi1#, Liqin Zhou2, Youguo Chen1✉, Xiuwu Tang1✉

1. Department of Gynecology & Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
2. Department of Gynecology & Obstetrics, Suzhou Xiangcheng People's Hospital, Suzhou 215006, Jiangsu Province, China.
#These authors contributed equally to this work.

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Li M, Chi C, Zhou L, Chen Y, Tang X. Circular PVT1 regulates cell proliferation and invasion via miR-149-5p/FOXM1 axis in ovarian cancer. J Cancer 2021; 12(2):611-621. doi:10.7150/jca.52234. Available from https://www.jcancer.org/v12p0611.htm

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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.

Keywords: PVT1, ovarian cancer, bioinformatics, circRNA, FOXM1