Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer

• Published in: Cell death & disease Vol. 9; no. 9; pp. 861 - 15
• Main Authors: Yong, Wu, Yu, Deng, Jun, Zhu, Yachen, Duan, Weiwei, Weng, Midie, Xu, Xingzhu, Ju, Xiaohua, Wu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-08-2018; Springer Nature B.V
• Subjects: 13; 13/1; 14/19; 38; 38/109; 38/71; 38/77; 42/89; 64/60; 82/80; Antibodies; Apoptosis - genetics; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Carcinogenesis - genetics; Carcinogenesis - pathology; Cell Biology; Cell Culture; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Disease Progression; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Humans; Immunology; Life Sciences; MicroRNAs - genetics; Middle Aged; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA-Binding Proteins - genetics; Therapeutic applications; Up-Regulation - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0908-z

The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our results showed that elevated NEAT1 expression in human HGSOC specimens correlated with a poor prognosis. Functional experiments demonstrated that knockdown of NEAT1 significantly prohibited ovarian cancer cell proliferation and invasion in vitro and restrained tumor growth in vivo. LIN28B was identified by bioinformatics analysis along with experimental evidence as a direct actor that enhanced NEAT1 stability. A rescue functional assay confirmed that the LIN28B/NEAT1 axis contributed to oncogenic functions in ovarian cancer cells. Moreover, gene expression profile data and dual luciferase reporter assay results demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for miR-506 to promote cell proliferation and migration. Taken together, our results showed that NEAT1, stabilized by LIN28B, promoted HGSOC progression by sponging miR-506. Thus, NEAT1 can be regarded as a vital diagnostic biomarker for HGSOC and a therapeutic target.