Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells.

Abstract

Long noncoding RNAs (lncRNAs) are increasingly recognized as functional regulators of human cancers. BRAF-activated noncoding RNA (BANCR), an oncogenic lncRNA, has a carcinogenic effect on many types of cancers. However, the clinical significance and molecular mechanisms of BANCR in cervical cancer are still unclear. Here, we generated BANCR knockout cell lines via CRISPR/Cas9 editing and revealed that BANCR plays roles in the apoptosis, proliferation, and migration of HeLa cells. A quantitative proteomics strategy was employed to globally identify BANCR-regulated proteins in HeLa cells. In total, we identified 569 differentially expressed proteins (DEPs) upon knockout of BANCR in HeLa cells. Bioinformatic analysis revealed that these DEPs were involved in diverse cellular pathways. Functional studies revealed that BANCR exerts its effects on the proliferation and apoptosis of HeLa cells through the regulation of cAMP-responsive element binding protein 1 (CREB1) expression. Mechanistically, BANCR could inhibit the expression of miR-582-5p, and CREB1 is a direct target of miR-582-5p; therefore, BANCR may exert its function by regulating CREB1 expression via targeting miR-582-5p in cervical cancer cells. Collectively, this study established a proteome-wide BANCR regulatory network, which provides novel insight into the molecular pathogenesis of cervical cancer and can serve as a basis for the development of targeted therapies.