长链非编码 RNA FLVCR1-AS1 通过调节 miR-513/YAP1 信号通路促进卵巢癌细胞的进展、迁移、侵袭和 EMT 过程。
LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer.
机构信息
Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Zhengzhou University, No. 7 Front Kangfu Street, Zhengzhou, 450052, Henan, People's Republic of China.
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
出版信息
J Exp Clin Cancer Res. 2019 Aug 14;38(1):356. doi: 10.1186/s13046-019-1356-z.
BACKGROUND
Long noncoding RNAs (lncRNAs) have been reported to be associated with the proliferation of several cancer cells. The aim of this study was to investigate the role of FLVCR1-AS1 in ovarian serous cancer (OSC).
METHODS
FLVCR1-AS1 expression was determined in human OSC tissues, serums and cell lines. The role of FLVCR1-AS1 knockdown or overexpression on OSC cell growth, migration, invasion, apoptosis and epithelial to mesenchymal transition (EMT) were evaluated in vitro using CCK8, colony formation assay, wound healing assay, transwell assay and western blot assay. Besides, luciferase reporter assays were performed to identify interactions among FLVCR1-AS1 and its target genes. Moreover, the in vivo effects were investigated using immunocompromised NSG female mice.
RESULTS
In this study, FLVCR1-AS1 expression was upregulated in OSC tissues, serums, and cells. Knockdown FLVCR1-AS1 decreased cell growth, migration, invasion, and EMT, as well as increased apoptosis in OSC cells, whereas, overexpression of FLVCR1-AS1 increased cell proliferation, migration, invasion, and EMT, and decreased apoptosis of OSC cells. Besides, FLVCR1-AS1 directly bound to miR-513 and downregulated its expression. Moreover, FLVCR1-AS1 reversed the effect of miR-513 on the OSC cell growth, which might be associated with the role of YAP1. Furthermore, in terms of mechanism, FLVCR1-AS1 promoted EMT in OSC cells. Finally, mice models further confirmed that knockdown FLVCR1-AS1 distinctly suppressed cell growth and EMT in vivo.
CONCLUSION
Taken together, FLVCR1-AS1 mediated miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in OSC cells.
背景
长链非编码 RNA（lncRNA）已被报道与多种癌细胞的增殖有关。本研究旨在探讨 FLVCR1-AS1 在卵巢浆液性癌（OSC）中的作用。
方法
检测人 OSC 组织、血清和细胞系中 FLVCR1-AS1 的表达。通过 CCK8、集落形成实验、划痕愈合实验、Transwell 实验和 Western blot 实验，评估 FLVCR1-AS1 敲低或过表达对 OSC 细胞生长、迁移、侵袭、凋亡和上皮间质转化（EMT）的影响。此外，还进行了荧光素酶报告实验，以确定 FLVCR1-AS1 与其靶基因之间的相互作用。此外，使用免疫缺陷 NSG 雌性小鼠进行体内研究。
结果
本研究发现，FLVCR1-AS1 在 OSC 组织、血清和细胞中表达上调。FLVCR1-AS1 敲低降低了 OSC 细胞的生长、迁移、侵袭和 EMT，并增加了细胞凋亡，而 FLVCR1-AS1 的过表达则增加了 OSC 细胞的增殖、迁移、侵袭和 EMT，并降低了细胞凋亡。此外，FLVCR1-AS1 可直接与 miR-513 结合并下调其表达。此外，FLVCR1-AS1 逆转了 miR-513 对 OSC 细胞生长的影响，这可能与 YAP1 的作用有关。此外，在机制方面，FLVCR1-AS1 促进了 OSC 细胞的 EMT。最后，小鼠模型进一步证实，FLVCR1-AS1 敲低显著抑制了体内细胞生长和 EMT。
结论
总之，FLVCR1-AS1 通过介导 miR-513/YAP1 信号通路促进 OSC 细胞的细胞进展、迁移、侵袭和 EMT 过程。
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