Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer.
Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer.
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受 LIN28B 调节的长非编码 RNA NEAT1 通过海绵 miR-506 促进高级别浆液性卵巢癌细胞增殖和迁移
DOI：
10.1038/s41419-018-0908-z
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发表时间：
2018-08-28
影响因子：
9
通讯作者：
Xiaohua W
中科院分区：
文献类型：
--
作者：
Yong W;Yu D;Jun Z;Yachen D;Weiwei W;Midie X;Xingzhu J;Xiaohua W
长非编码 RNA (lncRNA) 的异常表达在特定癌症中经常被报道，包括高级别浆液性卵巢癌 (HGSOC)。本研究的目的是探讨 HGSOC 中显着失调的 lncRNA (NEAT1) 的临床意义和潜在机制。我们的结果表明，人类 HGSOC 标本中 NEAT1 表达升高与不良预后相关。功能实验表明，敲除NEAT1可显着抑制体外卵巢癌细胞的增殖和侵袭，并抑制体内肿瘤的生长。通过生物信息学分析和实验证据确定 LIN28B 是增强 NEAT1 稳定性的直接作用者。救援功能测定证实 LIN28B/NEAT1 轴有助于卵巢癌细胞的致癌功能。此外，基因表达谱数据和双荧光素酶报告基因测定结果表明，NEAT1 可作为 miR-506 的竞争性内源 RNA (ceRNA)，促进细胞增殖和迁移。综上所述，我们的结果表明，由 LIN28B 稳定的 NEAT1 通过海绵 miR-506 促进 HGSOC 进展。因此，NEAT1 可以被视为 HGSOC 的重要诊断生物标志物和治疗靶点。
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.
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