Tumour suppressive long non-coding RNA AFDN-DT inhibits gastric cancer invasion via transcriptional regulation

Abstract

Emerging evidence has revealed that dysregulation of lncRNA is associated with the initiation and progression of cancer. However, the function of these lncRNAs in cancer remains largely unexplored. Here, we reported that AFDN-DT, an lncRNA that is repressed in gastric cancers (GC), functions as a tumour suppressor by inhibiting cell growth and metastasis through transcriptional repression of genes involved in metastasis. Using in vitro and in vivo models, we demonstrated that overexpression of AFDN-DT inhibited the proliferation and metastasis of GC. We found that AFDN-DT was located at the nucleus and interacted with the chromatin in gastric cells. Further, ChIRP-seq experiments and RNA-seq analysis revealed that AFDN-DT directly bound to the promoter regions and regulated the expression of genes essential for malignant transformation. Moreover, we demonstrated that DNA hypermethylation could repress AFDN-DT expression and treatment with DNA methylation inhibitors restored its expression. Collectively, the results of our study demonstrated the tumour suppressive role of AFDN-DT in GC and elucidated the transcription regulatory role of tumour suppressive lncRNAs, which can serve as potential prognostic markers for GC.

Keywords: AFDN divergent transcript; gastric cancer; lncRNA; transcriptional regulation.