LncRNA AGAP2-AS1 interacts with IGF2BP2 to promote bladder cancer progression via regulating LRG1 mRNA stability.

BACKGROUND:The long non-coding RNA (lncRNA) AGAP2-AS1 was implicated in tumorigenesis, yet with unclear mechanism in the development of Bladder Cancer (BCa). METHODS:We collected the clinicopathological features and tissue samples of 45 patients with BCa in Xiangya Hospital. Expressions of AGAP2-AS1 and LRG1 were detected by RT-qPCR in BCa tissues and normal tissues as well as in BCa cells. The roles of AGAP2-AS1 and LRG1 were investigated by CCK-8, colony formation assay, transwell assays and tube formation assay. The subcellular localization of AGAP2-AS1 was detected by Fluorescence in situ hybridization. Bioinformatics method, RNA immunoprecipitation, RNA pull-down assay and Actinomycin D test were used to predict and identify the relationships between AGAP2-AS1, LRG1 and IGF2BP2. Xenografted tumors were produced to explore the function of AGAP2-AS1 in BCa in vivo. RESULTS:AGAP2-AS1 and LRG1 were highly upregulated in BCa. AGAP2-AS1 positively correlated with T stage, grade and vascular invasion, but negatively correlated with the survival of patients. Overexpressions of AGAP2-AS1 promoted proliferation, migration, invasion, tumor angiogenesis in vitro and tumor growth, metastasis in vivo, knockdown of AGAP2-AS1 exhibited the opposite effects. AGAP2-AS1 localized mainly in the cytoplasm. AGAP2-AS1 directly bound to IGF2BP2 protein to enhance LRG1 mRNA stability. Inhibition of BCa progression by AGAP2-AS1 knockdown may be reversed by LRG1 overexpression. CONCLUSION:AGAP2-AS1 can promote BCa progression and metastasis by recruiting IGF2BP2 to stabilize LRG1.