Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Biomed Res Int. 2014;2014:384121. doi: 10.1155/2014/384121. Epub 2014 May 7.
Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.
先前，我们发现与相邻非癌性肝组织相比，肝癌福尔马林固定石蜡包埋（FFPE）组织中 microRNA-146a（miR-146a）的表达下调。在本研究中，我们探索了 miR-146a 对肝癌细胞恶性表型的体外影响。分光光度法、荧光法和荧光显微镜分别评估显示，miR-146a 模拟物可抑制 HepG2、HepB3 和 SNU449 肝癌细胞系的细胞生长并增加细胞凋亡。此外，Western blot 显示 miR-146a 模拟物下调 EGFR、ERK1/2 和 stat5 信号。与靶向 miR-146a 的已知靶基因 EGFR 的 siRNA 相比，这些作用较弱。此外，miR-146a 模拟物可增强各种 EGFR 靶向剂对细胞生长抑制和凋亡诱导的影响。最强的组合是 miR-146a 模拟物与西妥昔单抗，呈现协同作用。总之，miR-146a 在肝癌细胞的细胞生长和凋亡中发挥重要作用，诱导 miR-146a 水平可能是 HCC 的关键靶向分子治疗策略。
