AKAP8 interacting with DDX5 to regulate R-loop balance involves in lung carcinoma cell growth

Abstract

Triple-nucleotide chain of RNA:DNA hybrid structure R-loop is formed during transcription process which is closely associated with transcriptional regulation, transcriptional termination, epigenetic modifications, and structure of chromatin. Dysregulation of R-loop formation or resolution may disturb normal DNA replication or RNA transcription, leading to associated progress of disease. Herein, we found A-kinase-anchoring protein 8 (AKAP8) bind with R-loop structure in cell. Knock down of AKAP8 showed perturbation of balance of genomic R-loop formation and gene transcription. Evidences was shown that AKAP8 interacted with R-loop resolution protein ATP-dependent DEAD box RNA helicase DDX5 and increased chromatin associated DDX5 level. Finally, AKAP8 promoted UCP2 transcription and resolved R-loop level of its promoter region, and contributed to cell growth of adenocarcinomic human alveolar basal epithelial cell line A549, which may provide clues for poor prognosis of lung adenocarcinoma in high AKAP8 expression patients.