a Department of Clinical Laboratory , The Affiliated Dongtai Hospital of Nantong University , Dongtai , China.
b Department of Oncology , The Sixth People's Hospital of Yancheng City , Yancheng , Jiangsu , China.
Artif Cells Nanomed Biotechnol. 2018;46(sup1):159-167. doi: 10.1080/21691401.2017.1415918. Epub 2017 Dec 18.
Hepatocarcinoma is one of the most lethal malignancy haunting the Chinese population, which is partially due to the difficulties in diagnosis at an early stage. The search for a biomarker that could signify the presence and progress of hepatocarcinoma is never ended. MicroRNAs are 22-nt RNAs that could bind to 3' UTR of target mRNAs, mediating degradation of mRNAs or inhibiting the translation. Although much has been investigated, the role of miR-124 in hepatocarcinoma remained elusive. We first detected aberrant expression level of miR-124 in HCC tissues of 112 patients. By exploring the clinical parameters, we found a significantly inverse correlation between miR-124 level and TNM stages. Consistent with this, the survival analysis indicated the association of low miR-124 with longer survival time. Subsequent forced expression miR-124 resulted in reduced cell viability of Hep3B and SMMC-7221, which cell lines have high and low background expression of miR-124, respectively. TargetScan prediction rendered a subset of target candidates, which were selected for experimental validation, KLF4 was subject to luciferase assay. Ectopic expression of KLF4 increased the sphere formation ability and CD44/133-positive cell numbers, which can be reversed by abundant expression of miR-124, suggesting that KLF4 is a functional target of miR-124 in tumourigenesis and cancer progression of HCC.
肝癌是困扰中国人群的最致命恶性肿瘤之一,部分原因是早期诊断困难。寻找能够表示肝癌存在和进展的生物标志物的研究从未停止过。miRNAs 是 22nt 的 RNA,可以与靶 mRNA 的 3'UTR 结合,介导 mRNA 的降解或抑制翻译。尽管已经进行了大量研究,但 miR-124 在肝癌中的作用仍不清楚。我们首先检测了 112 例肝癌患者肝癌组织中 miR-124 的异常表达水平。通过探讨临床参数,我们发现 miR-124 水平与 TNM 分期之间存在显著的负相关。与此一致的是,生存分析表明 miR-124 低表达与更长的生存时间相关。随后强制表达 miR-124 导致 Hep3B 和 SMMC-7221 细胞活力降低,这两种细胞系分别具有高和低背景表达 miR-124。TargetScan 预测得到了一组靶候选物,选择进行实验验证,KLF4 是荧光素酶测定的对象。KLF4 的异位表达增加了球体形成能力和 CD44/133 阳性细胞数量,而 miR-124 的丰富表达可以逆转这种情况,表明 KLF4 是 miR-124 在肝癌发生和癌症进展中的功能性靶标。