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

Abstract

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.

An integrated analysis reveals the oncogenic function of lncRNA LINC00511 in human ovarian cancer

“…To date, a lot of ovarian cancer associated lncRNAs clinical relevance, biological function, and underlying mechanisms have been identified and reported. For example, overexpressed lncRNA NEAT1 is correlated with high‐grade serous ovarian cancer patients’ poor prognosis and promotes cell growth and migration through acting as a competing endogenous RNA for miR‐506 . In addition, Liang et al reported that lncRNA PTAR promotes cells invasion and metastasis by sponging miR‐101‐3p to release its repression of ZEB1 in serous ovarian cancer .…”

Long noncoding RNA CASC9 promotes LIN7A expression via miR‐758‐3p to facilitate the malignancy of ovarian cancer

“…Although without the potential to coding proteins, lncRNAs have been demonstrated to play vital functions in various biological processes, such as development and especially tumorigenesis (Ye et al, ; Zhu, Wang, Wu, et al, 2016). Amounting reports have shown that lncRNAs could regulate cell proliferation, differentiation, stemness, survival, and epithelial–mesenchymal transition (Q. Xu et al, ; Yong et al, ; Zhu, Wang, Huang, et al, 2016). For instance, Ren et al () showed that lncRNA CRNDE is upregulated in tongue squamous cell carcinoma tissues and enhances tumor cell proliferation and metastasis via inhibiting miR‐384.…”

Age at menarche and epithelial ovarian cancer risk: A meta‐analysis and Mendelian randomization study

“…Rs2153127, as one of instrumental variables of AAM in our MR study, is indicated to be associated with the expression of LIN28B in pituitary (https://www.gtexportal.org/home/snp/rs2153127). LIN28B was reported to be related to the proliferation, migration, and apoptosis of ovarian cancer . Further studies on variants associated with AAM or in the HPG axis may be beneficial to identify additional genetic variants for ovarian cancer risk.…”

“…LIN28B was reported to be related to the proliferation, migration, and apoptosis of ovarian cancer. 74,75 Further studies on variants associated with AAM or in the HPG axis may be beneficial to identify additional genetic variants for ovarian cancer risk. Additionally, the negative association between AAM and EOC risk could be explained by hormone-related "incessant ovulation" hypothesis, which supported increasing numbers of lifetime ovulations with higher risk of ovarian cancer.…”