Abstract
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.
Highlights
Bladder cancer (BC) is the ninth most malignant tumor worldwide, and approximately 430 000 cases were newly diagnosed in 2012 (Antoni et al, 2017)
The results revealed that PLOD1 can counteract the antitumor effects, in terms of cell migration and invasion, of miR-140-5p in BC cells, indicating that the PLOD1/ miR-140-5p axis plays an important role in BC development
Genes controlled by the miR-140-5p were found to be related to BC pathogenesis
Summary
Bladder cancer (BC) is the ninth most malignant tumor worldwide, and approximately 430 000 cases were newly diagnosed in 2012 (Antoni et al, 2017). BC is clinically divided into two groups: muscle-invasive BC (MIBC) and non-muscle-invasive BC (NMIBC) (Lemke and Shah, 2018). Patients with the latter have a favorable prognosis (5-year survival rate: approximately 90%) after surgical resection. Approximately 50% of cases develop intravesical recurrence after surgical resection, and approximately 15– 40% of recurrent BC cases are invasive and exhibit distant metastasis (Lemke and Shah, 2018). The survival of patients with distant metastasis is only 15 months due to no Abbreviations BC, bladder cancer; GEO, Gene Expression Omnibus; miRNA, microRNA; PLOD1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1; RISC, RNA-induced silencing complex; TCGA, The Cancer Genome Atlas
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call