RESUMO
This study is to elucidate the functions of miR-100 in hepatocellular carcinoma progression and to explore the underlying mechanisms. Expression levels of miR-100 in normal-cancer hepatocellular carcinoma tissues were measured using quantitative real-time PCR (qRT-PCR). The invasive and proliferative abilities of hepatocellular carcinoma cell lines transfected with mimic-NC or mimic-miR-100 were measured using transwell, CCK-8, and colony formation assays. The binding sites between CXCR7 and miR-100 were determined using luciferase reporter assays. The correlation of CXCR7 and miR-100 in hepatocellular carcinoma progression was further confirmed by cotransfection assays. Our results showed that miR-100 was significantly lower expressed in hepatocellular carcinoma tissues and negatively associated with CXCR7 expression. Cell functional assays' results found that upregulation of miR-100 inhibited the proliferative, invasive, and migrative abilities in hepatocellular carcinoma cells. Luciferase reporter assay suggested that CXCR7 mRNA and miR-100 bound one another. Increasing CXCR7 expression reversed the inhibitive effects of upregulated miR-100 in hepatocellular carcinoma cells. Further study showed that miR-100/CXCR7 played a role in hepatocellular carcinoma progression by regulating metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF). Conclusively, miR-100 exerts antitumor effects on hepatocellular carcinoma. Overexpression of miR-100 attenuates the invasive and proliferative abilities of hepatocellular carcinoma cells by targeting CXCR7.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Receptores CXCR/genética , Animais , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Estudos de Casos e Controles , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células Hep G2 , Hepatectomia , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Camundongos , Invasividade Neoplásica/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: MicroRNAs (miRNAs) are known to be involved in the pathogenesis of various cancers. The present study devotes efforts to discover the role of miR-128-3p in hepatocellular carcinoma (HCC). METHODS: MiR-128-3p and cell division cycle 6 (CDC6) expressions in HCC tissue (n = 50) and adjacent normal tissue (n = 50) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay and flow cytometry were applied to measure the viability and cell cycle distribution of HuH7 and HCCLM3 cells, respectively. The potential binding sites of miR-128-3p on CDC6 were predicted with Targetscan 7.2 and confirmed by dual-luciferase reporter assay. Expression analysis of CDC6 and survival analysis in HCC were performed by GEPIA2. Wound healing and Transwell assays were used to detect HCC cell migration and invasion, respectively. Expressions of miR-128-3p and epithelial-mesenchymal transition (EMT)-related proteins (MMP2, MMP9, E-Cadherin, N-Cadherin and Vimentin) were quantified using qRT-PCR and western blot, respectively. RESULTS: MiR-128-3p mRNA expression was lower in HCC tissue than in adjacent normal tissues. HCC cell viability was suppressed and cell cycle was arrested in G0/S phase by miR-128-3p mimic. CDC6 was targeted by miR-128-3p and had higher expression in HCC tissue. The promotive effects of overexpressed CDC6 on HCC cell viability, migration and invasion were reversed by up-regulating miR-128-3p. And the effects of overexpressed CDC6 on inhibiting E-Cadherin expression yet promoting MMP2, MMP9, N-Cadherin and Vimentin expressions in HCC cells were reversed by up-regulating miR-128-3p. CONCLUSION: MiR-128-3p may suppress HCC cell proliferation and metastasis via targeting CDC6.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Sequência de Bases , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Nucleares/genéticaRESUMO
Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR-660 while miR-660 targeted Bcl-2-associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR-660, which resulted in an upregulated expression of BAG5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR-660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305-mediated miR-660-5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Circular/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
MicroRNAs (miR) are single-stranded RNA of 21-23 nucleotides in length that repress mRNA translation and induces mRNA degradation. miR acts as an endogenous factor of gene expression and plays a crucial part in cancer biology such as cell development, proliferation, differentiation, and apoptosis. Numerous research has indicated that dysregulation of miR associates with colorectal carcinogenesis. In this review article, we firstly introduce the background of miR and colorectal cancer, and the mechanisms of miR in colorectal cancer, such as the proliferation, apoptosis, and progression. Then, we summarize the theranostic value of miR in colorectal cancer. Eventually, we discuss the potential directions and perspectives of miR. This article serves as a guide for further studies and implicate miR as a potent theranostic target for colorectal cancer.