Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, China.
Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Cancer Sci. 2018 May;109(5):1346-1356. doi: 10.1111/cas.13587. Epub 2018 Apr 22.
Metastasis-associated lung adenocarcinoma transcript 1 (malat1) is an oncogenic long non-coding RNA (lncRNA) which has been proven to be associated with various types of tumors. Transcription factor specificity protein 1 (SP1) is overexpressed in many types of cancers. Previously, we observed that malat1 expression level is regulated by SP1 in lung cancer. In the present study, we found that transfection of expression construct of malat1 5' end fragment M5 enhances stability and transcriptional activity of SP1. Various SP1 target genes are also upregulated following overexpression of malat1 M5 in lung adenocarcinoma cells. We also showed that malat1 M5 interacts with the C-terminal domain of SP1 by RNA immunoprecipitation (RIP) assay coupled with UV cross-linking. Malat1-SP1 association results in increase of SP1 stability. In turn, SP1 promotes malat1 transcription, thus forming a positive feedback loop. In conclusion, our data show that in lung adenocarcinoma cells, malat1 interacts with SP1 protein and promotes SP1-mediated transcriptional regulation of SP1 target genes.
转移相关肺腺癌转录物 1(MALAT1)是一种致癌性的长非编码 RNA(lncRNA),已被证明与多种类型的肿瘤有关。转录因子特异性蛋白 1(SP1)在许多类型的癌症中过表达。以前,我们观察到 MALAT1 的表达水平受肺癌中 SP1 的调控。在本研究中,我们发现 MALAT1 5'端片段 M5 的表达构建体的转染增强了 SP1 的稳定性和转录活性。在肺腺癌细胞中过表达 MALAT1 M5 后,各种 SP1 靶基因也被上调。我们还通过 RNA 免疫沉淀(RIP)测定与 UV 交联偶联显示 MALAT1 M5 与 SP1 的 C 端结构域相互作用。MALAT1-SP1 相互作用导致 SP1 稳定性增加。反过来,SP1 促进 MALAT1 转录,从而形成正反馈环。总之,我们的数据表明,在肺腺癌细胞中,MALAT1 与 SP1 蛋白相互作用,并促进 SP1 介导的 SP1 靶基因的转录调控。