Long non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 promotes lung adenocarcinoma by directly interacting with specificity protein 1

• Published in: Cancer science Vol. 109; no. 5; pp. 1346 - 1356
• Main Authors: Li, Shufeng, Ma, Fang, Jiang, Kunpeng, Shan, Haitao, Shi, Minke, Chen, Baojun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-05-2018; John Wiley and Sons Inc
• Subjects: 3' Untranslated Regions; A549 Cells; Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Animal welfare; Animals; Antibodies; Binding Sites; Cell growth; Cell Line, Tumor; Feedback, Physiological; Female; Gene Expression Regulation, Neoplastic; Gene regulation; Humans; Immunoprecipitation; Laboratory animals; lncRNA; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; malat1; Male; Medical prognosis; Metastases; Metastasis; Mice; Middle Aged; Neoplasm Staging; Neoplasm Transplantation; Non-coding RNA; Original; Patients; Plasmids; Proteins; Ribonucleic acid; RNA; RNA Stability; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; SP1; Sp1 protein; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; Survival Analysis; transcription; Transcription factors; Transcription, Genetic; Transfection; Tumors; Up-Regulation; United States > US; China; lung cancer; lncRNA; transcription; SP1; malat1
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13587

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.
In A549 and H1299 cells, overexpression of malat1 increased SP1 stability. In turn, SP1 transcriptionally regulated malat1, thus forming a positive feedback loop and promoted SP1 target gene expression, which was involved in malignant transformation and carcinogenesis.