Upregulation of lncRNA DARS‐AS1 accelerates tumor malignancy in cervical cancer by activating cGMP‐PKG pathway

Abstract This paper investigates the function of lncRNA DARS‐AS1 in cervical cancer (CC) as well as its in‐depth mechanism. The differential expression of DARS‐AS1 and ATP1B2 were analyzed based on The Cancer Genome Atlas and the Genotype‐Tissue Expression databases, and the survival rate was measured using Kaplan–Meier survival analysis. Biological function experiments were performed to detect cell proliferation, invasion, and migration. Quantitative real‐time polymerase chain reaction was carried out to detect the expression of DARS‐AS1 and ATP1B2. Western blot analysis was utilized to assess the protein levels of ATP1B2 and cGMP‐PKG pathway‐related proteins. DARS‐AS1 was expressed at high levels in CC tissues and cell lines, and high expression of DARS‐AS1 indicated a lower survival rate. CCK‐8 and colony formation assays revealed that the overexpression of DARS‐AS1 promoted the proliferation of CC cells. Furthermore, bioinformatics analysis suggested that the cGMP‐PKG pathway ranks as the first pathway enriched by the differential genes that correlated with DARS‐AS1 (| r | > 0.4). ATP1B2, as a cGMP‐PKG pathway‐related gene, was significantly correlated with the overall survival of CC patients. We further confirmed that ATP1B2 was lowly expressed in CC and negatively correlated with the DARS‐AS1 expression. Then, biological function experiments exhibited that the promotion of cell proliferation, invasion, and migration resulted due to the upregulation of DARS‐AS1 could be canceled by ATP1B2 overexpression. Finally, Western blot revealed that upregulation of DARS‐AS1 could activate the cGMP‐PKG pathway, while overexpression of ATP1B2 reversed this activation. Our study revealed that DARS‐AS1/ATP1B2 contributes to regulating the progression of CC at least partially by modulating the cGMP‐PKG pathway.