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长链非编码 RNA SNHG15/miR-18a-5p 轴通过激活 Akt/mTOR 信号通路促进卵巢癌细胞增殖。

The lncRNA SNHG15/miR-18a-5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway.

机构信息

The Fourth Department of Gynaecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shengyang, Liaoning, China.

出版信息

J Cell Biochem. 2020 Dec;121(12):4699-4710. doi: 10.1002/jcb.29474. Epub 2020 Aug 15.

Abstract

Here, we report the expression pattern, function and regulatory mechanism of SNHG15 together with miR-18a-5p micro RNA in ovarian cancer (OC) for the first time. We recruited 20 patients and took normal ovarian tissues and ovarian tumor tissues from them. We used cell culture, transfection, in vivo tumor xenograft assay, and multiple types of detection assays to investigate the expression and regulation of long noncoding RNA (lncRNA) SNHG15/miR-18a-5p in ovarian tissues and cells. Results: We found that the messenger RNA expression level of SNHG15 was significantly higher and miR-18 was decreased in ovarian cancer tissues and in OC cells. Functional experiments showed that SNHG15 overexpression potentiated the migration and invasion of OC cells, while SNHG15 inhibition reduced the tumor proliferation, which was restored via overexpression of miR-18a. SNHG15 was found to directly target and suppress the expression of miR-18a. Our results illustrate the possible molecular mechanism of lncRNA SNHG15/miR-18a-5p functions in cell proliferation in OC. SNHG15/miR-18a promoted the progression of OC cells via the protein kinase B/mammalian target of rapamycin signaling pathway.

摘要

在这里,我们首次报道了 SNHG15 及其微小 RNA-18a-5p 在卵巢癌(OC)中的表达模式、功能和调控机制。我们招募了 20 名患者,从他们身上采集了正常卵巢组织和卵巢肿瘤组织。我们使用细胞培养、转染、体内肿瘤异种移植实验和多种检测方法来研究长链非编码 RNA(lncRNA)SNHG15/miR-18a-5p 在卵巢组织和细胞中的表达和调节。结果:我们发现 SNHG15 的信使 RNA 表达水平在卵巢癌组织和 OC 细胞中显著升高,而 miR-18 则降低。功能实验表明,SNHG15 的过表达增强了 OC 细胞的迁移和侵袭能力,而 SNHG15 的抑制则减少了肿瘤的增殖,这可以通过 miR-18a 的过表达来恢复。SNHG15 被发现可以直接靶向并抑制 miR-18a 的表达。我们的结果说明了 lncRNA SNHG15/miR-18a-5p 在 OC 细胞增殖中的可能分子机制。SNHG15/miR-18a 通过蛋白激酶 B/哺乳动物雷帕霉素靶蛋白信号通路促进 OC 细胞的进展。

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