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

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.