Aberrantly expressed PLOD1 promotes cancer aggressiveness in bladder cancer: a potential prognostic marker and therapeutic target.
Bladder cancer (BC) is the ninth most malignant tumor worldwide. Some BC patients will develop muscle-invasive BC (MIBC), which has a 5-year survival rate of approximately 60% due to metastasis. As such, there is an urgent need for novel therapeutic and diagnostic targets for MIBC. Analysis of novel antitumor microRNA (miRNA)-mediated cancer networks is an effective strategy for exploring therapeutic targets and prognostic markers in cancers. Our previous miRNA analysis revealed that miR-140-5p acts as an antitumor miRNA in BC cells. Here, we investigated miR-140-5p regulation of BC molecular pathogenesis. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) was found to be directly regulated by miR-140-5p, and aberrant expression of PLOD1 was observed in BC clinical specimens. High PLOD1 expression was significantly associated with a poor prognosis (disease-free survival: P = 0.0204; overall survival: P = 0.000174). Multivariate analysis showed PLOD1 expression to be an independent prognostic factor in BC patients (hazard ratio = 1.51, P = 0.0099). Furthermore, downregulation of PLOD1 by siRNAs and a specific inhibitor significantly decreased BC cell aggressiveness. Aberrant expression of PLOD1 was closely associated with BC pathogenesis. In summary, the present study showed that PLOD1 may be a potential prognostic marker and therapeutic target for BC.
['Yamada|Yasutaka|Y|', 'Kato|Mayuko|M|', 'Arai|Takayuki|T|', 'Sanada|Hiroki|H|', 'Uchida|Akifumi|A|', 'Misono|Shunsuke|S|', 'Sakamoto|Shinichi|S|', 'Komiya|Akira|A|', 'Ichikawa|Tomohiko|T|', 'Seki|Naohiko|N|']
D014408:Biomarkers, Tumor D045744:Cell Line, Tumor D018572:Disease-Free Survival D005260:Female D018507:Gene Expression Regulation, Developmental D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D035683:MicroRNAs D009363:Neoplasm Proteins D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase D012334:RNA, Neoplasm D015996:Survival Rate D001749:Urinary Bladder Neoplasms
PLOD1 bladder cancer microRNA miR-140-5p inhibitor passenger strand