LINC00852 Promotes Lung Adenocarcinoma Spinal Metastasis by Targeting S100A9

论文信息

题目：《LINC00852 Promotes Lung Adenocarcinoma Spinal Metastasis by Targeting S100A9》（译：《LINC00852 通过靶向 S100A9 促进肺腺癌的脊柱转移》）
Abstract：Background: Lung adenocarcinoma has a strong tendency to develop into bone metastases, especially spinal metastases (SM). Long noncoding RNAs (lncRNAs) play critical roles in regulating several biological processes in cancer cells. However, the mechanisms underlying the roles of lncRNAs in the development of SM have not been elucidated to date.Methods: Clinical specimens were collected for analysis of differentially expressed lncRNAs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to examine the effects of these genes on pathways. RNA pull-down was utilized to identify the targeting protein of lncRNAs. The effects of lncRNA on its target were detected in A549 and SPCA-1 cells via perturbation of the lncRNA expression. Oncological behavioral changes in transfected cells and phosphorylation of kinases in the relevant pathways, with or without inhibitors, were observed. Further, tumorigenicity was found to occur in experimental nude mice.Results: LINC00852 and the mitogen-activated protein kinase (MAPK) pathway were found to be associated with SM. Moreover, the LINC00852 target S100A9 had a positive regulatory role in the progression, migration, invasion, and metastasis of lung adenocarcinoma cells, both in vitro and in vivo. Furthermore, S100A9 strongly activated the P38 and REK1/2 kinases, and slightly activated the phosphorylation of the JNK kinase in the MAPK pathway in A549 and SPCA-1 cells.Conclusion: LINC00852 targets S100A9 to promote progression and oncogenic ability in lung adenocarcinoma SM through activation of the MAPK pathway. These findings suggest a potential novel target for early intervention against SM in lung cancer.（译：背景：肺腺癌有向骨转移的趋势，尤其是脊柱转移。长非编码rna（lncRNAs）在肿瘤细胞的多种生物学过程中起着重要的调控作用。然而，lncRNAs在SM发生发展中的作用机制至今尚未阐明。方法：收集临床标本进行差异表达lncRNAs的分析。京都基因和基因组百科全书（KEGG）被用来研究这些基因对通路的影响。RNA下拉法鉴定lncRNAs的靶向蛋白。在A549和SPCA-1细胞中通过干扰lncRNA的表达来检测lncRNA对靶细胞的作用。观察转染细胞的肿瘤学行为改变以及相关途径中激酶的磷酸化，无论是否使用抑制剂。结果：LINC00852和丝裂原活化蛋白激酶（MAPK）通路与SM有关。此外，LINC00852靶点S100A9在体外和体内对肺腺癌细胞的进展、迁移、侵袭和转移具有积极的调节作用。此外，S100A9在A549和SPCA-1细胞中强烈激活P38和REK1/2激酶，并轻微激活MAPK途径中JNK激酶的磷酸化。结论：LINC00852通过激活MAPK途径靶向S100A9促进肺腺癌SM的进展和致癌能力。这些发现为肺癌早期干预提供了一个新的靶点。）
期刊：Journal of Cancer
Impact Factor: 3.249
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研究作者：刘鹏
研究单位：上海中山医院骨科
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