Abstract
Lactate dehydrogenase A (LDHA) is overexpressed in various cancers. We investigated LDHA expression and function in bladder cancer. We demonstrate that LDHA is up-regulated in bladder cancer cells and promotes proliferation, invasion, and glycolysis. Additionally, we found that microRNA (miR)-200c directly targets LDHA in bladder cancer cells. Ectopic expression of miR-200c inhibited LDHA-induced glycolysis, cell proliferation, and invasion. Thus, targeting LDHA through miR-200c is a potential therapeutic strategy in bladder cancer.
Highlights
Bladder cancer is the leading genitourinary malignancy [1]
We demonstrate that Lactate dehydrogenase A (LDHA) is up-regulated in bladder cancer cells and promotes proliferation, invasion, and glycolysis
We found that LDHA was up-regulated in bladder cancer tissue (Figure 1A, left)
Summary
Bladder cancer is the leading genitourinary malignancy [1]. There were an estimated 76,960 new cases and 16,390 bladder cancer-related deaths in the United States in 2016 [2]. Approximately 75% of new cases are noninvasive subtypes, the recurrence rate is high following local treatment [3]. MiRNAs bind to highly conserved, complementary sequences in the 3′-untranslated regions (3′-UTRs) of target mRNAs and inhibit protein translation. MiRNAs can regulate gene expression by inducing degradation of target mRNAs [5]. MiR-200c regulates epithelialto-mesenchymal transition (EMT) and chemosensitivity [8, 9]. Dysregulation of miR-200c has been observed in several cancers including gastric [10], breast [11], and renal cell carcinoma [12]
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