Abstract
Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer mortality in the world [1,2]
The results suggested that upregulation of miR-184 promoted the proliferation and tumorigenicity of HCC cells in vitro
The anchorage-independent growth assay showed similar results (Figure 5D, Figure S4D). These results suggested that silencing SOX7 expression in miR-184-repressed cells could reverse the inhibitory effect of the miR-184 inhibitor on HCC cell proliferation
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer mortality in the world [1,2]. Due to the high morbidity of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, the incidence of HCC is higher in Asian countries. The HCC incidence is much higher in China than in other Asian countries, and Chinese cases account for 55% of all HCC cases worldwide [2]. The absence of routine screening means that most HCC cases in China are initially diagnosed at advanced stages, and patients die from tumor growth or liver failure [3]. The late onset of clinical symptoms accounts for the late diagnosis and poor prognosis; the identification of reliable biomarkers for HCC is especially important [4]. Further studies on the biology involved in HCC initiation and progression are urgently needed to develop effective diagnostic methods and therapeutic strategies
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