4.7 Article

Long intergenic noncoding RNA LINC00284 knockdown reduces angiogenesis in ovarian cancer cells via up-regulation of MEST through NF-κB1

期刊

FASEB JOURNAL
卷 33, 期 11, 页码 12047-12059

出版社

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201900101RR

关键词

mesoderm-specific transcript; proliferation; apoptosis; tumorigenicity

资金

  1. National Science Foundation of China [81771548]

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Ovarian cancer (OC) is one of the major causes of cancer-related mortality in women worldwide. Long noncoding RNAs might play a role as oncogenes or tumor suppressors. Therefore, we investigated the effect and underlying mechanisms of long intergenic noncoding RNA (LINC00) 284 on angiogenesis in OC cells. Expression of LINC00284 in OC tissues and cells was determined. Next, the interaction between LINC00284 and mesoderm-specific transcript (MEST) was evaluated. Subsequently, OC cells were transfected with overexpressed (oe)-LINC00284, silenced (si)-LINC00284, si-NF-kappa B1, oe-MEST, or si-MEST plasmids to investigate the underlying mechanism of LINC00284 in OC. Afterwards, the expression of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated protein x (Bax), VEGF, and CD31 was determined to assess the effect of LINC00284 on OC cell proliferation, invasion, migration angiogenesis, and apoptosis. Finally, the effect of LINC00284 on tumorigenesis was investigated in nude mice models of OC. LINC00284 was highly expressed in OC. si-LINC00284 increased expression of MEST. si-LINC00284 or si-NF-kappa B1 led to the reduction in cell proliferation, migration, invasion, tube formation, angiogenesis, and tumorigenic ability and promoted apoptosis in OC by down-regulating MMP-2, MMP-9, Bcl-2, VEGF, and CD31 and up-regulating Bax. These effects were all reversed following the si-MEST. In vivo experiments found the same results, confirming the aforementioned findings. Taken together, LINC00284 is involved in angiogenesis during OC development by recruiting NF-kappa B1 and down-regulating MEST.-Ruan, Z., Zhao, D. Long intergenic noncoding RNA LINC00284 knockdown reduces angiogenesis in ovarian cancer cells via up-regulation of MEST through NF-kappa B1.

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