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

LINC00441 promotes cervical cancer progression by modulating miR-450b-5p/RAB10 axis
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DOI:
10.1186/s12935-020-01400-x
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发表时间:
2020-08-04
影响因子:
5.8
通讯作者:
Liu, Xuejie
Liu, Xuejie
中科院分区:
医学2区
文献类型:
--
作者:
Han, Haiyan;Shao, Qingchun;Liu, Xuejie

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宫颈癌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。越来越多的证据表明,长链非编码rna (lncRNAs)在包括CC在内的癌症中是至关重要的生物学功能调节剂,而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尚不清楚。方法采用qRT-PCR方法检测CC组织或细胞中基因的表达情况。采用CCK-8、菌落形成、流式细胞术、transwell、western blot及动物实验等方法分析LINC00441在CC中的功能,采用荧光素酶报告基因、RIP和RNA拉下实验验证指示基因之间的结合关系。结果LINC00441在CC组织和细胞中表达上调。此外,LINC00441缺失抑制了体外细胞增殖和运动以及体内肿瘤生长。LINC00441可以海绵miR-450b-5p上调RAB10的表达。最后,miR-450b-5p抑制剂或RAB10上调可抵消LINC00441敲低介导的CC发展功能。结论LINC00441通过靶向miR-450b-5p/RAB10轴驱动CC进展,可能为研究CC相关分子机制提供新的思路。
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.