Long intergenic noncoding RNA LINC00284 knockdown reduces angiogenesis in ovarian cancer cells via up-regulation of MEST through NF-κB1
Long intergenic noncoding RNA LINC00284 knockdown reduces angiogenesis in ovarian cancer cells via up-regulation of MEST through NF-κB1
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DOI：
10.1096/fj.201900101rr
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发表时间：
2019-11-01
期刊：
影响因子：
4.8
通讯作者：
Zhao, Dong
中科院分区：
文献类型：
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作者：
Ruan, Zhengyi;Zhao, Dong
卵巢癌（OC）是全世界女性癌症相关死亡的主要原因之一。长链非编码 RNA 可能发挥癌基因或肿瘤抑制基因的作用。因此，我们研究了长基因间非编码RNA (LINC00) 284对OC细胞血管生成的影响和潜在机制。测定了 OC 组织和细胞中 LINC00284 的表达。接下来，评估了 LINC00284 和中胚层特异性转录物 (MEST) 之间的相互作用。随后，用过表达的 (oe)-LINC00284、沉默的 (si)-LINC00284、si-NF-kappa B1、oe-MEST 或 si-MEST 质粒转染 OC 细胞，以研究 LINC00284 在 OC 中的潜在机制。然后，测定基质金属蛋白酶（MMP）-2、MMP-9、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关蛋白x（Bax）、VEGF和CD31的表达，以评估LINC00284对OC细胞增殖、侵袭、迁移血管生成和凋亡的影响。最后，在OC裸鼠模型中研究了LINC00284对肿瘤发生的影响。 LINC00284 在 OC 中高表达。 si-LINC00284 增加了 MEST 的表达。 si-LINC00284或si-NF-kappa B1通过下调MMP-2、MMP-9、Bcl-2、VEGF和CD31以及上调Bax，导致OC中细胞增殖、迁移、侵袭、管形成、血管生成和致瘤能力降低，并促进细胞凋亡。 si-MEST 后，这些影响全部被逆转。体内实验也发现了相同的结果，证实了上述发现。总而言之，LINC00284 通过招募 NF-kappa B1 和下调 MEST 参与 OC 发育过程中的血管生成。-Ruan, Z.、Zhao, D。长基因间非编码 RNA LINC00284 敲低通过 NF-kappa B1 上调 MEST，从而减少卵巢癌细胞中的血管生成。
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.