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LINC00441通过调控miR-450b-5p/RAB10轴促进宫颈癌进展。

LINC00441 promotes cervical cancer progression by modulating miR-450b-5p/RAB10 axis.

作者信息

Han Haiyan, Shao Qingchun, Liu Xuejie

机构信息

Reproductive Center, Affiliated Hospital of Weifang Medical College, No. 2428 Yuhe Road, Kuiwen District, Weifang, 261031 Shandong China.

Obstetrical Department 1, Affiliated Hospital of Weifang Medical College, No. 2428 Yuhe Road, Kuiwen District, Weifang, 261031 Shandong China.

出版信息

Cancer Cell Int. 2020 Aug 4;20:368. doi: 10.1186/s12935-020-01400-x. eCollection 2020.

Abstract

BACKGROUND

As one of the most common gynaecological malignant tumors, cervical cancer (CC) has become an important public health issue. Emerging evidence has revealed long non-coding RNAs (lncRNAs) are crucial regulators of biological functions in cancers, including CC. And the oncogenic role of LINC00441 has been verified in hepatocellular carcinoma (HCC). But the molecular mechanism and biological functions of LINC00441 in CC remain unknown.

METHODS

qRT-PCR analysis detected the expression of genes in CC tissues or cells. CCK-8, colony formation, flow cytometry, transwell, western blot assays as well as animal studies were conducted to analyze the function of LINC00441 in CC. Luciferase reporter, RIP and RNA pull down assays were applied to verify the binding relations among the indicated genes.

RESULTS

LINC00441 was upregulated in CC tissues and cells. Further, LINC00441 depletion repressed cell proliferation and motility in vitro as well as tumor growth in vivo. LINC00441 could sponge miR-450b-5p to upregulate RAB10 expression. Finally, miR-450b-5p inhibitor or RAB10 upregulation counteracted LINC00441 knockdown-mediated function on the development of CC.

CONCLUSIONS

LINC00441 drives CC progression by targeting miR-450b-5p/RAB10 axis, which might provide new idea for researching CC-related molecular mechanism.

摘要

背景

宫颈癌(CC)作为最常见的妇科恶性肿瘤之一,已成为一个重要的公共卫生问题。新出现的证据表明,长链非编码RNA(lncRNA)是包括CC在内的癌症生物学功能的关键调节因子。LINC00441在肝细胞癌(HCC)中的致癌作用已得到证实。但LINC00441在CC中的分子机制和生物学功能仍不清楚。

方法

qRT-PCR分析检测CC组织或细胞中基因的表达。进行CCK-8、集落形成、流式细胞术、Transwell、蛋白质免疫印迹分析以及动物研究,以分析LINC00441在CC中的功能。应用荧光素酶报告基因、RNA免疫沉淀(RIP)和RNA下拉分析来验证所示基因之间的结合关系。

结果

LINC00441在CC组织和细胞中上调。此外,LINC00441的缺失在体外抑制细胞增殖和迁移,并在体内抑制肿瘤生长。LINC00441可以吸附miR-450b-5p以上调RAB10的表达。最后,miR-450b-5p抑制剂或RAB10的上调抵消了LINC00441敲低介导的对CC发展的作用。

结论

LINC00441通过靶向miR-450b-5p/RAB10轴驱动CC进展,这可能为研究CC相关分子机制提供新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b04b/7409438/af89610c837b/12935_2020_1400_Fig1_HTML.jpg

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