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[This retracts the article DOI: 10.3892/ol.2020.11852.].
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Hepatocellular carcinoma (HCC), a major primary liver cancer, is one of the most lethal malignancies worldwide. Increasing evidence has demonstrated that chromobox protein homolog 3 (CBX3) functions as an oncogene in different cancers. However, its expression profiles and biological functions in HCC remain unknown. Data on CBX3 expression in HCC acquired from the GEO and TCGA databases were analyzed. The biological functions of CBX3 in HCC were examined by in vitro experiments. Bioinformatics analysis, qRT-PCR and western blotting were performed to explore the mechanism of CBX3 in HCC. CBX3 mRNA was upregulated in HCC tissues, and overexpression of CBX3 mRNA was negatively correlated with malignancies and poor prognosis in HCC patients. CBX3 knockdown decreased growth, migration and invasion of HCC cells in vitro. Moreover, bioinformatics analysis and experimental observation indicated that CBX3 expression was correlated with cell cycle regulatory proteins in HCC cells. Finally, starBase predicted that miR-139 could directly target CBX3 in HCC. Confirmatory experiments verified that miR-139 overexpression attenuated HCC cell proliferation and migration, and these effects could be reversed by overexpressing CBX3. Our results showed that the miR-139/CBX3 axis may be involved in HCC development by regulating cell cycle progression and may be a promising target in the treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Divisão Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA MensageiroRESUMO
To date, the role of hematopoieticsubstrate1associated protein X1 (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 logrank test. The target genes for HAX1 was predicted by TargetScan and verified by a dualluciferase reporter assay. The protein and mRNA expressions of HAX1 in liver cancer and adjacent noncancerous tissues were examined by immunohistochemistry and reverse transcriptionquantitative PCR (RTqPCR). The transfection efficiency of HAX1, small interfering RNA against HAX1, microRNA (miR)125a mimics, miR125a inhibitor, miR223 mimics and miR223 inhibitor in liver cancer cells was determined by RTqPCR. The expression of HAX1, p53, VEGF, epithelialtomesenchymal transition (EMT)related markers (Ecadherin, Ncadherin and vimentin) in the cancer cells were determined by western blotting and RTqPCR. Cell viability, migration, invasion and colony formation rates were determined by Cell Counting Kot8, 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. miR125a5p directly binds to HAX1. Upregulation of miR125a5p expression inhibited cell viability, migration, invasion and colony formation of SKHep1 cells and reduced the expression of HAX1, VEGF, Ncadherin and vimentin, but increased cell apoptosis and the expression of p53 and Ecadherin. However, the effects miR125a5p upregulation were partially reversed by SKHep1 cells with HAX1 overexpression. Downregulated miR125a5p in SNU387 cells produced opposite effects, which was partially reversed by HAX silencing. In conclusion, miR125a5p suppresses liver cancer growth via targeting HAX1 and concurrently modulating the expression of p53 and VEGF and EMTrelated markers.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/genética , Sequência de Bases , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Prognóstico , Ensaio Tumoral de Célula-Tronco , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vimentina/metabolismoRESUMO
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.
