{'fraction_non_alphanumeric': 0.036455059710873663, 'fraction_numerical': 0.0339409176618479, 'mean_word_length': 5.368, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
miR‐199b‐5p directly targets PODXL and DDR1 and decreased levels of miR‐199b‐5p correlate with elevated expressions of PODXL and DDR1 in acute myeloid leukemia

Aberrant expression of Podocalyxin (PODXL), a CD34 orthologue, has been associated with acute myeloid leukemia (AML). Herein, via tissue microarray, we discovered elevated PODXL expression in M2, M4 and M1 FAB-subtype patients. Importantly, various investigations have linked aberrant miRNA expression with AML (1). A miRNA prediction algorithm identified PODXL as a conserved target for miR-199b, a significantly down-regulated miRNA in AML. Further prediction of miR-199b-5p targets identified Discoidin domain receptor 1 (DDR1) as another highly conserved target. For the first time, IHC analyses showed that DDR1 levels were also highly up-regulated in AML and more significantly, were elevated in the same AML cases where PODXL levels were increased. Experimental validation (via-mimics) confirmed that both PODXL and DDR1 are targets of miR-199b-5p. Furthermore, 3’UTR-luciferase assays established that miR-199b-5p targets PODXL and DDR1. Most importantly, we found significant decrease in miR-199b-5p levels in most AML patients with elevated PODXL and DDR1 expressions. Importantly, overexpression of miR-199b-5p in K562 cells caused significant decrease in collagen IV induced migration. Taken together, our studies have identified concurrent increased expression of PODXL and DDR1 in AML and directly connect decreased miR-199b-5p to these novel targets and potential antigomir-mediated therapeutic implications in AML.