LINC00152 knockdown exerts repressive effects on epithelial-mesenchymal transition in bladder cancer.

Bladder cancer (BLCA) is a prevalent malignancy of the urinary tract. Long noncoding RNAs (lncRNAs) exert significant effects on various human cancers by targeting microRNAs (miRs). This study, therefore, probed the action of the LINC00152/miR-103a-3p axis in epithelial-mesenchymal transition (EMT) and progression of BLCA. LINC00152, miR-103a-3p, and ADORA3 expression in clinical BLCA tissues were tested. LINC00152 was knocked down in BLCA cells alone or combined with miR-103a-3p inhibition or ADORA3 overexpression. The level of EMT- and PI3K/AKT pathway-related genes was assessed with Western blot. Cell proliferation, invasion and migration, and apoptosis were examined with CCK8 and EdU, Transwell, and flow cytometry assays, respectively. Binding of miR-103a-3p to LINC00152 and ADORA3 was validated through RIP and dual-luciferase reporter gene assays. The action of LINC00152 in BLCA progression was verified in vivo. LINC00152 and ADORA3 expression was abundant and miR-103a-3p expression was poor in BLCA tissues. LINC00152 knockdown or PI3K/AKT pathway inhibition repressed malignant behaviors and EMT of BLCA cells. Mechanistically, LINC00152 bound specifically to miR-103a-3p, which targeted ADORA3 and then activated the PI3K/AKT pathway. miR-103a-3p inhibition or ADORA3 overexpression nullified the suppressive impacts of LINC00152 knockdown on EMT and malignant behaviors of BLCA cells. Furthermore, LINC00152 knockdown decreased ADORA3 expression and suppressed tumor growth in vivo. LINC00152 knockdown upregulates miR-103a-3p to reduce ADORA3 expression, thus protecting against the malignant biological behaviors and EMT of BLCA cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00829-0.