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.

中文翻译：

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异常表达的PLOD1促进膀胱癌的癌症侵袭性：一种潜在的预后标志物和治疗靶标。

膀胱癌（BC）是全球第九大恶性肿瘤。一些BC患者会发展成肌肉侵袭性BC（MIBC），由于转移，其5年生存率约为60％。因此，迫切需要MIBC的新型治疗和诊断靶标。分析新型抗肿瘤微RNA（miRNA）介导的癌症网络是探索癌症的治疗靶点和预后标志物的有效策略。我们以前的miRNA分析显示，miR-140-5p在BC细胞中起着抗肿瘤miRNA的作用。在这里，我们研究了BC分子发病机制的miR-140-5p调控。发现前胶原赖氨酸，2-氧戊二酸5-双加氧酶1（PLOD1）直接受miR-140-5p调节，并且在BC临床标本中观察到PLOD1的异常表达。PLOD1高表达与不良预后显着相关（无疾病生存期：P = 0.0204；总生存期：P = 0.000174）。多变量分析表明，PLOD1表达是BC患者的独立预后因素（危险比= 1.51，P = 0.0099）。此外，siRNA和特异性抑制剂对PLOD1的下调显着降低了BC细胞的侵袭性。PLOD1的异常表达与BC发病机理密切相关。总而言之，本研究表明PLOD1可能是BC的潜在预后标志物和治疗靶标。siRNA和特异性抑制剂对PLOD1的下调显着降低了BC细胞的侵袭性。PLOD1的异常表达与BC发病机理密切相关。总而言之，本研究表明PLOD1可能是BC的潜在预后标志物和治疗靶标。siRNA和特异性抑制剂对PLOD1的下调显着降低了BC细胞的侵袭性。PLOD1的异常表达与BC发病机理密切相关。总而言之，本研究表明PLOD1可能是BC的潜在预后标志物和治疗靶标。