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miR-563 通过靶向 LIN28B 抑制人肺癌细胞增殖。

MiR-563 restrains cell proliferation via targeting LIN28B in human lung cancer.

机构信息

Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China.

出版信息

Thorac Cancer. 2020 Jan;11(1):55-61. doi: 10.1111/1759-7714.13257. Epub 2019 Nov 25.

Abstract

BACKGROUND

Previous investigations have revealed that miR-563 is associated with a number of diseases including the ossification of posterior longitudinal ligament, Parkinson's disease or drug resistance to leukemia. Yet, the role of miR-563 and its molecular mechanism in the initiation and progression of cancers has not been previously explored. In this study, we aimed to provide clues to the function of miR-563 and its direct target in lung cancer.

METHODS

Online informatics software was applied to predict the target genes of miR-563. MiR-563 targeting LIN28B was evaluated through the luciferase reporter gene analysis. The effect of miR-563 on LIN28B at the level of RNA and protein was detected using RT-PCR and immunoblotting. The ability of proliferation of human lung cancer A549 was examined by MTT assay. RNA interference targeting LIN28B was examined through immunoblotting. The level of miR-563 and LIN28B and their correlation were analyzed in 27 cases of lung tumor tissues by real-time PCR.

RESULTS

Oncogenic LIN28B was identified as one of the target genes of miR-563 in lung cancer cells. MiR-563 dose-dependently decreased the LIN28B RNA level and subsequently its protein level in the cells. Cell proliferation was suppressed by ectopic miR-563 expression and was accelerated after endogenous miR-563 was knocked down by its inhibitor. However, silence in LIN28B reversed promotion of cell proliferation by the inhibition of miR-563. In lung cancer tissues, miR-563 was decreased and negative correlation of miR-563 and LIN28B was shown.

CONCLUSION

MiR-563 plays a tumor suppressive role in lung cancer progression via targeting oncogenic LIN28B.

摘要

背景

先前的研究表明,miR-563 与多种疾病有关,包括后纵韧带骨化、帕金森病或白血病耐药。然而,miR-563 及其在癌症发生和发展中的分子机制尚未被探索。在这项研究中,我们旨在为 miR-563 及其在肺癌中的直接靶基因的功能提供线索。

方法

在线信息学软件用于预测 miR-563 的靶基因。通过荧光素酶报告基因分析评估 miR-563 对 LIN28B 的靶向作用。使用 RT-PCR 和免疫印迹检测 miR-563 对 LIN28B 在 RNA 和蛋白质水平上的影响。通过 MTT 测定法检测人肺癌 A549 细胞的增殖能力。通过免疫印迹检测针对 LIN28B 的 RNA 干扰。通过实时 PCR 分析 27 例肺癌组织中 miR-563 和 LIN28B 的水平及其相关性。

结果

致癌 LIN28B 被鉴定为肺癌细胞中 miR-563 的靶基因之一。miR-563 剂量依赖性地下调细胞中的 LIN28B RNA 水平,随后下调其蛋白水平。外源性 miR-563 表达抑制细胞增殖,而其抑制剂下调内源性 miR-563 后加速细胞增殖。然而,沉默 LIN28B 逆转了 miR-563 抑制对细胞增殖的促进作用。在肺癌组织中,miR-563 降低,miR-563 和 LIN28B 呈负相关。

结论

miR-563 通过靶向致癌 LIN28B 在肺癌进展中发挥肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450f/6938763/70a80a6bb51c/TCA-11-55-g001.jpg

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