In summary, by combining RNA sequencing and functional investigation, we discovered that lnc-STYK1-2 acts as a new tumor suppressor of bladder cancer that repressed bladder cancer cell proliferation, migration, invasion, and tumorigenesis by targeting miR-146b-5p to modulate ITGA2 and the ATK/STAT3/NF-kB signaling pathway. The gene discussed is STAT3; the disease is urinary bladder cancer.