Abstract. acts as an oncomiR and is involved in tumor development, progression and metastasis, and confers resistance to chemotherapeutic drugs by targeting a number of molecules in several human cancers. However, the function and underlying molecular mechanism of miR-494 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we determined the role played by miR-494 in HCC tissues and HCC cell lines using quantitative RT-PCR (RT-qPCR). The results showed that, miR-494 was significantly upregulated in HCC tissues and HCC cell lines. Additionally, a high miR-494 expression positively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Luciferase reporter assays confirmed that miR-494 binds to the 3'-untranslated region (3'-UTR) of the phosphatase and tensin homolog (PTEN) mRNA and represses its translation. Functional analyses indicated that the upregulation of miR-494 promoted cell viability, migration and invasion, decreased cell apoptosis and cell cycle arrest at G1 stage, and conferred sorafenib resistance to HCC cell lines. Underexpression of PTEN by siRNA significantly attenuated the inhibitory effects of anti-miR-494 on the proliferation, migration and invasion of liver cancer cells. Mechanistic investigations revealed that miR-494 suppressed the expression of PTEN but increased the expression of PI3K and p-Akt, which contribute to the promotion of proliferation, migration and invasion, and increased sorafenib resistance to HCC cell lines. These findings suggested that miR-494 is a potential candidate for HCC therapeutics.

Small nucleolar RNA host gene 15 (SNHG15) is a long noncoding RNA (lncRNA), which promotes progression of multiple cancers. Its specific function in hepatocellular carcinoma (HCC), however, is uncertain. The aims of our study were, therefore, to explore the role of SNHG15 in HCC. SNHG15 and miR-141-3p expression were assessed via quantitative real-time PCR (qRT-PCR) in 58 paired HCC samples and adjacent matched adjacent normal tissues. CCK-8 assay, flow cytometric examination, and wound healing/invasion assays were used to respectively assess how SNHG15 influences cell proliferation, the cell cycle, and the migratory and invasive potential of HCC cells. MicroRNA (miRNAs) that targeted SNHG15 was screened by Starbase2.0 and identified by RNA immunoprecipitation and luciferase reporter assays. SNHG15 expression was markedly increased, whereas miR-141-3p expression was substantially reduced in HCC cells and tissue samples relative to normal controls. When SNHG15 was knocked down, this resulted in a significant disruption to the proliferation, as well as the invasive and migratory ability of these HCC cells. miR-141-3p was also found to be an SNHG15 target in HCC cells. Furthermore, miR-141-3p inhibitor partially reversed the observed SNHG15 depletionmediated reduction in HCC proliferation, migration, and invasion. By repressing miR-141-3p, SNHG15 could modulate zinc finger E-box binding homeobox 2 (ZEB2) and E2F transcription factor 3 (E2F3) expression, both of which are miR-141-3p targets. These finding suggested that SNHG15 promoted HCC progression via negative regulation of miR-141-3p, thus identifying a potential novel HCC treatment pathway. K E Y W O R D S hepatocellular carcinoma, lncRNA, miR-141-3p, SNHG15

MicroRNAs, considered as a promising focus for the treatment of tumors, are key regulators of a large number of genes. The aim of the present study was to investigate the biological functions of microRNA (miR)-330-3p in liver cancer as it had been identified previously that miR-330-3p was deregulated in liver cancer. In order to identify the function of miR-330-3p in liver cancer, the expression of miR-330-3p was determined in liver cancer tissues and adjacent non-tumor tissues using reverse transcription-quantitative polymerase chain reaction analysis. To elucidate the function of miR-330-3p in liver cancer, miR-330-3p was overexpressed using mimic transfection. Cell migration was inhibited by miR-330-3p in liver cancer cells. The miRNA target prediction databases were used to identify potential target genes of miR-330-3p in liver cancer. The RNA level of mitogen-activated protein kinase kinase 1 (MAP2K1) was downregulated by miR-330-3p in liver cancer cells. In conclusion, miR-330-3p suppresses cell migration by targeting MAP2K1 in liver cancer cells.

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.

Hepatocellular carcinoma (HCC) is known as a frequent type of primary cancer in the liver, and it is the third‐most common cause of cancer‐related death all over the world. However, the molecular mechanism in the progression of HCC is still unclear. The current study was designed to investigate the expression and function of microRNA‐34a (miR‐34a) in HCC. In HCC tissues and cells, the expression levels of miR‐34a were analyzed by quantitative real‐time polymerase chain reaction. The association between the level of miR‐34a and hexokinase (HK)‐1 was also investigated via luciferase reporter assay. Cell viability and proliferation were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and flow cytometry. To assess whether miR‐34a can limit tumor growth in vivo, animal models and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used for examining the role of miR‐34a on the development of HCC and cell apoptosis. The expression level of miR‐34a was reduced in HCC samples and cells. The expression of miR‐34a was associated with the viability and proliferation capacity of HCC cells, and miR‐34a could inhibit HCC cells proliferation by inhibiting HK1. In the mouse model of HCC, volumes and weight of the tumors were significantly decreased by transfection with miR‐34a mimic compared with the control group. Furthermore, miR‐34a mimics could induce apoptosis in a greater proportion of cells compared with the control group. Taken together, the data may provide some novel insights into the molecular mechanism of miR‐34a and HK1 in the progression of HCC. Thus, miR‐34a/HK1 axis might be a novel promising therapeutic target for treating HCC.