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Liver cancer is one of the most common and aggressive tumors, and usually leads to a poor clinical outcome. Increasing evidence has demonstrated the important functions of microRNAs (miRs) in tumor progression. miR-574-3p has been reported as a tumor suppressor and potential therapeutic target in various types of cancer. However, the underlying mechanism of the effects of miR-574-3p in liver cancer remains unknown. In the present study, reverse transcription-quantitative PCR was performed to detect miR-574-3p expression in liver cancer tissues, and the influence of miR-574-3p on cell growth was evaluated using the Cell Counting Kit-8 assay, and cell migration and flow cytometry analyses. The present study revealed that miR-574-3p expression was downregulated in liver cancer tissues and cell lines. miR-574-3p overexpression, achieved by transfecting miR-574-3p mimics into liver cancer cells, reduced cell proliferation and migration, and promoted cell apoptosis. Mechanistically, ADAM metallopeptidase domain 28 (ADAM28) was identified as a miR-574-3p target via binding to the 3'-untranslated region of the ADAM28 mRNA. Gain-of-function of miR-574-3p downregulated the expression levels of ADAM28 in liver cancer cells. Additionally, overexpression of ADAM28 significantly attenuated the suppressive effect of miR-574-3p on the growth of liver cancer cells. The present results provide novel insights into the function of the miR-574-3p/ADAM28 signaling pathway in liver cancer.

To date, the role of hematopoietic-substrate-1-associated protein X-1 (HAX1) in liver cancer is rarely studied. The present study explored the role of HAX1 in liver cancer. The association between HAX1 expression and survival of patients with liver cancer was analyzed by a log-rank test. The target genes for HAX1 was predicted by TargetScan and verified by a dual-luciferase reporter assay. The protein and mRNA expressions of HAX1 in liver cancer and adjacent non-cancerous tissues were examined by immunohistochemistry and reverse transcription-quantitative PcR (RT-qPcR). The transfection efficiency of HAX1, small interfering RNA against HAX1, microRNA (miR)-125a mimics, miR-125a inhibitor, miR-223 mimics and miR-223 inhibitor in liver cancer cells was determined by RT-qPcR. The expression of HAX1, p53, VEGF, epithelial-to-mesenchymal transition (EMT)-related markers (E-cadherin, N-cadherin and vimentin) in the cancer cells were determined by western blotting and RT-qPcR. cell viability, migration, invasion and colony formation rates were determined by cell counting Kot-8, wound healing, Transwell and colony formation assays, respectively. The results showed that high expression of HAX1 in liver cancer was found relate to poor prognosis in patients with liver cancer, and upregulation of HAX1 expression in liver cancer tissues was related to lower overall survival. miR-125a-5p directly binds to HAX1. Upregulation of miR-125a-5p expression inhibited cell viability, migration, invasion and colony formation of SK-Hep1 cells and reduced the expression of HAX1, VEGF, N-cadherin and vimentin, but increased cell apoptosis and the expression of p53 and E-cadherin. However, the effects miR-125a-5p upregulation were partially reversed by SK-Hep1 cells with HAX1 overexpression. downregulated miR-125a-5p in SNU-387 cells produced opposite effects, which was partially reversed by HAX silencing. In conclusion, miR-125a-5p suppresses liver cancer growth via targeting HAX1 and concurrently modulating the expression of p53 and VEGF and EMT-related markers.

Background Hepatocellular carcinoma (HCC), comprises of the major primary liver cancer, is one of the most lethal malignancies in the world [1]. Increasing evidence has demonstrated that chromobox protein homolog 3 (CBX3) functioned as an oncogene in different cancers. However, its expression profiles and biological functions in HCC remain exactly unknown. Methods Data of CBX3 expression in HCC acquired from TCGA and GEO databases were analyzed. The biological functions of CBX3 in HCC were examined by in vitro experiments. Bioinformatics analysis, qRT-PCR and western blot were performed to explpore the mechanism of CBX3 involved in HCC. Results CBX3 mRNA was upregulated in HCC tissues, and overexpression of CBX3 mRNA was negatively correlated with malignancies and poor prognosis in HCC patients. Knocking down of CBX3 induced slower growth, less migration and fewer invasions of the HCC cells in vitro. Moreover, bioinformatics analysis and experimental observation indicated that CBX3 expression was correlated with cell cycle regulation proteins of HCC cells. Finally, Starbase predicted that the miR-139 could directly target CBX3 in HCC; Confirmatory experiments verified that miR-139 overexpression attenuated the HCC cells proliferation and migration, which could be reversed by overexpressing CBX3 concurrently. Conclusion Our results concluded that miR-139/CBX3 axis may involve in the HCC development through regulating cell cycle progression and may be a promising target in the treatment of HCC.

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