Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Oncol Rep. 2013 Jul;30(1):17-24. doi: 10.3892/or.2013.2443. Epub 2013 May 9.
The prognosis of gallbladder cancer (GBC) remains poor despite recent advances in diagnostics and therapeutic strategies. Although the role of microRNAs (miRs) in GBC have not been well documented, miR-155 is known to be associated with inflammation-associated carcinogenesis in various types of cancers. The aim of this study was to investigate the clinical significance of miR-155 expression and the biological functions of miR-155 in GBC. The expression levels of miR-155 in surgically resected GBCs and gallbladders with pancreaticobiliary maljunction (PBM) were assessed by quantitative reverse transcription-polymerase chain reaction. The relationship between the expression levels of miR-155 and clinicopathological features of GBCs was analyzed. Human GBC cell lines were transfected with miR-155 inhibitors or mimics, and the effects on proliferation and invasion were assessed. miR-155 was significantly overexpressed in GBCs when compared with that in gallbladders with PBM (p=0.007) and normal gallbladders (p=0.04). The high expression level of miR-155 in GBCs was significantly associated with the presence of lymph node metastasis (p=0.01) and a poor prognosis (p=0.02). In vitro assays showed that aberrant expression of miR-155 significantly enhanced GBC cell proliferation and invasion. In conclusion, high miR-155 expression correlates with the aggressive behavior of GBCs, and miR-155 may become a prognostic marker and therapeutic target for GBC.
尽管在诊断和治疗策略方面取得了最近的进展,但胆囊癌 (GBC) 的预后仍然很差。尽管 microRNAs (miRs) 在 GBC 中的作用尚未得到很好的记录,但已知 miR-155 与各种类型癌症中的炎症相关致癌作用有关。本研究旨在探讨 miR-155 表达的临床意义及其在 GBC 中的生物学功能。通过定量逆转录聚合酶链反应评估手术切除的 GBC 和伴有胰胆管汇合异常 (PBM) 的胆囊中 miR-155 的表达水平。分析 miR-155 的表达水平与 GBC 临床病理特征之间的关系。用人 GBC 细胞系转染 miR-155 抑制剂或模拟物,评估对增殖和侵袭的影响。与伴有 PBM 的胆囊 (p=0.007) 和正常胆囊 (p=0.04) 相比,miR-155 在 GBC 中显著过表达。GBC 中 miR-155 的高表达水平与淋巴结转移的存在 (p=0.01) 和预后不良 (p=0.02) 显著相关。体外实验表明,miR-155 的异常表达显著增强了 GBC 细胞的增殖和侵袭。总之,高 miR-155 表达与 GBC 的侵袭性行为相关,miR-155 可能成为 GBC 的预后标志物和治疗靶点。