Wang Liang, Wu Jinhong, Xie Changao
Department of Hepatobiliary Pancreatic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Iran J Basic Med Sci. 2017 Jul;20(7):783-790. doi: 10.22038/IJBMS.2017.9010.
MicroRNAs (miRNAs) are considered as powerful, post-transcriptional regulators of gene expression in hepatocellular carcinoma cells (HCC). However, the function of miR-92a is still unclear in HCC.
Expression of miR-92a in human HCC cell lines was evaluated using qRT-PCR. MTT assay and transwell assay were used to examine the function of miR-92a in HepG2 and Huh7 cells. Bioinformatic analyses and luciferase reporter assays were used to validate FOXA2 as a direct target gene of miR-92a. Consistently, the biological outcome of miR-92a on regulating FOXA2 was examined by proliferation and invasion analysis .
Here, we detected the higher expression of miR-92a in human HCC cell lines, such as HepG2, Huh7 and Hep3B, compared with the normal human hepatocyte L02 cells. Overexpression of miR-92a significantly increased cell growth and invasion ability, while the knockdown of miR-92a could remarkably inhibit the growth and invasion possibility. We identified that miR-92a has specific targeting sites in the 3'-UTR of the FOXA2. By overexpressing miR-92a in HepG2 cells or Huh7 cells, the expression of FOXA2 was remarkably repressed.
We demonstrated that miR-92a may play a critical role in HCC proliferation and invasion and may serve as a novel therapeutic target by the repression of FOXA2.
微小RNA(miRNA)被认为是肝细胞癌细胞(HCC)中基因表达强大的转录后调节因子。然而,miR-92a在肝癌中的功能仍不清楚。
采用qRT-PCR评估miR-92a在人肝癌细胞系中的表达。采用MTT法和Transwell法检测miR-92a在HepG2和Huh7细胞中的功能。通过生物信息学分析和荧光素酶报告基因检测验证FOXA2是miR-92a的直接靶基因。同样,通过增殖和侵袭分析检测miR-92a对FOXA2调控的生物学结果。
在此,我们检测到与正常人肝细胞L02细胞相比,miR-92a在人肝癌细胞系如HepG2、Huh7和Hep3B中表达较高。miR-92a的过表达显著增加细胞生长和侵袭能力,而miR-92a的敲低可显著抑制生长和侵袭可能性。我们确定miR-92a在FOXA2的3'-UTR中有特定的靶向位点。通过在HepG2细胞或Huh7细胞中过表达miR-92a,FOXA2的表达显著受到抑制。
我们证明miR-92a可能在肝癌增殖和侵袭中起关键作用,并可能通过抑制FOXA2作为一种新的治疗靶点。