Background and aim: Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is abnormally expressed in various human malignancies, including hepatocellular carcinoma (HCC). Let-7b is a miRNA with the effect of a tumor suppressor gene, and its expression level in various tumor tissues is lower than that in normal tissues. Studies have found that IGF-1R can be abnormally activated in the process of hepatocyte deterioration, and the expression level of IGF-1R in HCC is significantly up-regulated. The aim of this study was to investigate the functional mechanism of NEAT1/let-7b-IGF-1R axis in HCC.
Methods: The expressions of NEAT1 and microRNA (miR)-let-7b in HCC tissues and cell lines were quantified by quantitative real-time PCR (qRT-PCR). The effect of NEAT1 on tumor growth was observed in a mice model of transplanted hepatoma. The effects of down-regulation or up-regulation of NEAT1 expression in HCC cell lines were analysed from the perspectives of cell viability and apoptosis. The binding sites of NEAT1 and miR-let-7b were predicted by biological software. The expression of the miR-let-7b target molecules IGF-1R was detected by Western blotting.
Results: The results showed that the expressions of NEAT1 were significantly increased, while the expressions of miR-let-7b were decreased in the HCC tissues and cell lines. Additionally, it was found that the expressions of NEAT1 and miR-let-7b showed a negative correlation in HCC tissues. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited the tumor growth. Meanwhile, the cell viability of HepG2/Huh7 cell lines was significantly decreased via the downregulation of NEAT1, whereas the corresponding rates of apoptosis were significantly increased. It was further proven that there was a certain negative regulatory mechanism between NEAT1 and miR-1et-7b, which was related to the expression of IGF-1R.
Conclusion: The over-expression of NEAT1 could promote the proliferation of HCC cells by inhibiting the expression of the miR-let-7b regulated by IGF-1R.
Keywords: long non-coding RNA NEAT1, microRNA-let-7b, hepatocellular carcinoma, IGF-1R, transplanted hepatoma mice model