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非编码 RNA LOXL1-AS1 通过调控 miR-18b-5p/VMA21 轴在卵巢癌中发挥致癌作用。

Non-coding RNA LOXL1-AS1 exhibits oncogenic activity in ovarian cancer via regulation of miR-18b-5p/VMA21 axis.

机构信息

Department of Gynaecology and Obstetrics, Jinan Maternal and Child Health Hospital Jinan, Shandong 250012, PR China.

Infertility Center, Department of Gynaecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.

出版信息

Biomed Pharmacother. 2020 May;125:109568. doi: 10.1016/j.biopha.2019.109568. Epub 2020 Feb 10.

Abstract

Long non-coding RNAs (lncRNAs) exert critical effects in the process of malignant cancers and lncRNA LOXL1 Antisense RNA 1 (LOXL1-AS1) has been demonstrated to be a pro-oncogene in multiple tumor types. In the current study, we illuminated the precise roles of LOXL1-AS1 in the development of ovarian cancer. LOXL1-AS1 is significantly overexpressed in ovarian carcinoma tissue compared with adjacent non-cancerous sample. The luciferase reporter gene assay reveals the relationship between LOXL1-AS1 and miR-18b-5p, miR-18b-5p and its target gene, Vacuolar ATPase Assembly Factor VMA21 (VMA21). Transfection of LOXL1-AS1 siRNA or miR-18b-5p mimics inhibits the growth and aggressive phenotypes of SKOV3 and OVCAR3 cell. Furthermore, miR-18b-5p suppresses ovarian carcinoma cell proliferation and metastasis by targeting VMA21 and LOXL1-AS1 regulates ovarian carcinoma cell growth and metastasis through sponging miR-18b-5p. These findings suggest that lncRNA LOXL1-AS1 promotes ovarian cancer cell growth, migratory and invasiveness via modulating miR-18b-5p/VMA21 axis.

摘要

长链非编码 RNA(lncRNA)在恶性肿瘤的发生过程中发挥着重要作用,并且 lncRNA LOXL1 反义 RNA 1(LOXL1-AS1)已被证明是多种肿瘤类型的癌基因。在本研究中,我们阐明了 LOXL1-AS1 在卵巢癌发展中的精确作用。与相邻的非癌样本相比,LOXL1-AS1 在卵巢癌组织中显著过表达。荧光素酶报告基因实验揭示了 LOXL1-AS1 与 miR-18b-5p、miR-18b-5p 与其靶基因 Vacuolar ATPase Assembly Factor VMA21(VMA21)之间的关系。转染 LOXL1-AS1 siRNA 或 miR-18b-5p 模拟物可抑制 SKOV3 和 OVCAR3 细胞的生长和侵袭表型。此外,miR-18b-5p 通过靶向 VMA21 抑制卵巢癌细胞的增殖和转移,而 LOXL1-AS1 通过海绵吸附 miR-18b-5p 调节卵巢癌细胞的生长和转移。这些发现表明,lncRNA LOXL1-AS1 通过调节 miR-18b-5p/VMA21 轴促进卵巢癌细胞的生长、迁移和侵袭。

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