EGR1/LINC00839/SOX5 axis modulates migration, invasion and Gemcitabine resistance of bladder cancer cells

Abstract

ABSTRACT Background Bladder cancer is one of the most common malignant tumors of the urinary system, and its incidence is increasing worldwide. However, the underlying mechanisms that trigger migration, invasion and chemotherapy resistance are unclear. Results Bioinformatics analysis of bladder cancer cohort indicated that LINC00839 is deregulated in bladder cancer. LINC00839 was validated and highly expressed in bladder cancer patients and cell lines. In addition, LINC00839 induced the migration, invasion and Gemcitabine resistance of bladder cancer cells. We identified that the transcription factor EGR1 directly repressed LINC00839 and thereby suppressed the migration and invasion of bladder cancer cells. Furthermore, LINC00839 interacted with miR-142, which subsequently regulated the expression of SOX5, a well-studied oncogene and targeted by miR-142. In addition, EGR1 served as a suppressive transcription factor of SOX5. Therefore, EGR1 directly or indirectly regulates SOX5 via LINC00839/miR-142 axis. LINC00839 induced Gemcitabine resistance by promoting autophagy. Conclusions EGR1, LINC00839/miR-142 and SOX5 form a coherent feed-forward loop that modulates the migration, invasion and Gemcitabine resistance of bladder cancer.