Background: Deregulation of FSCN1 has been observed in human cancers. However, the regulatory mechanism of FSCN1 in hepatocellular carcinoma (HCC) remains largely unknown.
Aims: Our study aimed to reveal the roles of microRNA (miR)-133a, miR-145, and FSCN1 in HCC cells.
Methods: Real-time RT-PCR and western blot were performed to determine the expression of miR-133a, miR-145, and FSCN1. Luciferase reporter assay was used to determine whether FSCN1 was a target of miR-133a and miR-145. Effects of miR-133a, miR-145, and FSCN1 on HCC cell proliferation, apoptosis, migration, and invasion were then investigated.
Results: We showed that the expression of FSCN1 was increased in HCC tissues compared to the normal adjacent tissues. Moreover, upregulation of FSCN1 and downregulation of miR-145 and miR-133a co-existed in HCC. Functional studies revealed that miR-145 and miR-133a negatively regulated the expression of FSCN1 in HCC cells, via directly binding to the 3'-untranslational region of FSCN1 mRNA. Overexpression of miR-145 and miR-133a led to decreased FSCN1 expression, and downregulation of miR-145 and miR-133a resulted in increased FSCN1 expression in HCC cells. Furthermore, overexpression of miR-145 and miR-133a inhibited cellular proliferation, migration, and invasion, while promoted apoptosis in HCC cells. On the contrary, inhibition of miR-145 and miR-133a promoted cellular proliferation, migration, and invasion, while suppressed apoptosis in HCC cells.
Conclusion: Our study suggests that the abnormal upregulation of FSCN1 in HCC is associated with downregulation of miR-145 and miR-133a, and miR-145 and miR-133a inhibit malignant progression of HCC in vitro, possibly via directly targeting FSCN1.
Keywords: FSCN1; Hepatocellular carcinoma; MicroRNA-133a; MicroRNA-145.