miR-124 inhibits progression of hepatocarcinoma by targeting KLF4 and promises a novel diagnostic marker

<p>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.</p>