Long non-coding RNA LINC00630 facilitates hepatocellular carcinoma progression through recruiting transcription factor E2F1 to up-regulate cyclin-dependent kinase 2 expression

This study is aimed to investigate the role of long non-coding RNA 630 (LINC00630) in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC00630 expression in HCC cell lines and tissues. After LINC00630 was overexpressed or depleted in HCC cell lines, cell counting kit-8 (CCK-8) assay, BrdU assay, and flow cytometry were conducted for detecting HCC cell multiplication, apoptosis, and cell cycle progression. The catRAPID database was adopted to predict the binding relationship between LINC00630 and E2F transcription factor 1 (E2F1), and RNA pull-down and RNA immunoprecipitation (RIP) assays were carried out to verify this binding relationship. The binding of E2F1 to the cyclin-dependent kinase 2 (CDK2) promoter region was verified by dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assay. Western blotting was conducted to detect the protein expression of E2F1 and CDK2 in HCC cells. We report that LINC00630 expression was up-regulated in HCC and was significantly correlated with TNM stage and lymph node metastasis. LINC00630 overexpression facilitated HCC cell proliferation and cell cycle progression and inhibited the cell apoptosis, while LINC00630 knockdown had the opposite effects. LINC00630 directly bounds with E2F1. LINC00630 overexpression enhanced the binding of E2F1 to the CDK2 promoter region, thereby promoting CDK2 transcription, whereas knocking down LINC00630 inhibited CDK2 transcription. Collectively, LINC00630 promoted CDK2 transcription by recruiting E2F1 to the promoter region of CDK2, thereby promoting the malignant progression of HCC. Our data suggest that LINC00630 is a promising molecular target for HCC.