MicroRNA-548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein 1

MicroRNA-548b通过直接靶向特异性蛋白1抑制肝癌细胞的增殖和侵袭

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作者:Haile Qiu, Gehong Zhang, Bin Song, Junmei Jia

Abstract

Emerging studies have revealed that microRNAs (miRNAs) are aberrantly expressed in hepatocellular carcinoma (HCC), and the dysregulation of miRNAs exerts crucial roles in the carcinogenesis and development of HCC. Therefore, elucidating the relationship between miRNAs and HCC progression is of great importance to develop novel therapeutic techniques and to improve the prognosis of patients with this malignancy. Recently, miR-548b-3p (miR-548b) has been demonstrated to be a cancer-associated miRNA in tongue squamous cell carcinoma and glioma. However, the expression and function of miR-548b in HCC remain poorly understood. In the present study, it was found that miR-548b is expressed at low levels in HCC tissues and cell lines. Decreased miR-548b expression was found to be positively associated with the clinical features of HCC, including the TNM stage and lymph node metastasis. Functional experiments revealed that upregulation of miR-548b expression decreased proliferation and invasion of HCC cells. Specificity protein 1 (SP1) was verified to be a direct target of miR-548b in HCC cells; as Spearman's correlation analysis identified miR-548b expression to be negatively correlated with that of SP1 expression in HCC tissue specimens. In addition, SP1 inhibition exhibited similar effects as miR-548b overexpression in HCC cells. SP1 reintroduction significantly reversed the suppressive effects of miR-548b upregulation on the proliferation and invasion of HCC cells. In conclusion, the results presented in the present study demonstrated that miR-548b may serve as a tumor suppressive miRNA that inhibits the proliferation and invasion of HCC cells by directly targeting SP1. Consequently, miR-548b can be exploited as a novel therapeutic target for treating patients with HCC in the future, but this needs to be investigated further.

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