LINC00852 Promotes Lung Adenocarcinoma Spinal Metastasis by Targeting S100A9
LINC00852 Promotes Lung Adenocarcinoma Spinal Metastasis by Targeting S100A9
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DOI：
10.7150/jca.26897
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Dong, Jian
中科院分区：
文献类型：
--
作者：
Liu, Peng;Wang, Houlei;Dong, Jian
背景：肺腺癌有很强的向骨转移的倾向，尤其是脊柱转移瘤（SM）。长链非编码RNA（IncRNA）在调节癌细胞的多种生物学过程中起关键作用。然而，潜在的作用机制的IncRNA在发展中的SM.Methods：临床标本收集的差异表达的IncRNA进行分析的SM至今尚未阐明。使用基因和基因组的京都百科全书（KEGG）来检查这些基因对途径的影响。利用RNA pull-down技术鉴定IncRNA的靶蛋白。在A549和SPCA-1细胞中，通过干扰IncRNA的表达来检测IncRNA对其靶标的影响。观察到转染细胞的肿瘤学行为变化和相关通路中激酶的磷酸化，有或没有抑制剂。结果：LINC 00852和丝裂原活化蛋白激酶（MAPK）通路与SM相关。此外，LINC 00852靶点S100 A9在肺腺癌细胞的进展、迁移、侵袭和转移中具有正性调节作用，无论是在体外还是在体内。结论：LINC 00852通过激活MAPK信号通路，以S100 A9为靶点，促进肺腺癌SM的发生发展和致瘤能力。这些发现为肺癌SM的早期干预提供了一个潜在的新靶点。
Background: Lung adenocarcinoma has a strong tendency to develop into bone metastases, especially spinal metastases (SM). Long noncoding RNAs (IncRNAs) play critical roles in regulating several biological processes in cancer cells. However, the mechanisms underlying the roles of IncRNAs in the development of SM have not been elucidated to date.Methods: Clinical specimens were collected for analysis of differentially expressed IncRNAs. 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 IncRNAs. The effects of IncRNA on its target were detected in A549 and SPCA-1 cells via perturbation of the IncRNA 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.