RESUMO
The phosphoinositide 3-kinase pathway is one of the most commonly altered pathways in human cancers. The serum/glucocorticoid-regulated kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK1, SGK2, and SGK3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. Few studies have investigated the role of SGK2 in hepatocellular carcinoma. Here, we report that SGK2 expression levels were upregulated in hepatocellular carcinoma tissues and human hepatoma cell lines compared to the adjacent normal liver tissues and a normal hepatocyte line, respectively. We found that downregulated SGK2 inhibits cell migration and invasive potential of hepatocellular carcinoma cell lines (SMMC-7721 and Huh-7).We also found that downregulated SGK2 suppressed the expression level of unphosphorylated (activated) glycogen synthase kinase 3 beta. In addition, SGK2 downregulation decreased the dephosphorylation (activation) of ß-catenin by preventing its proteasomal degradation in the hepatocellular carcinoma cell lines. These findings suggest that SGK2 promotes hepatocellular carcinoma progression and mediates glycogen synthase kinase 3 beta/ß-catenin signaling in hepatocellular carcinoma cells.
Assuntos
Carcinoma Hepatocelular/genética , Glicogênio Sintase Quinase 3 beta/genética , Proteínas Imediatamente Precoces/genética , Neoplasias Hepáticas/genética , Proteínas Serina-Treonina Quinases/genética , beta Catenina/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Transdução de SinaisRESUMO
Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been confirmed to be involved in the progression of various cancers; however, its mechanism of action in osteosarcoma has not been well addressed. In our study, TUG1 was overexpressed and miR-153 was downregulated in osteosarcoma tissues and cell lines. A loss-of-function assay showed that TUG1 knockdown suppressed the viability, colony formation, and invasion of osteosarcoma cells in vitro. Moreover, TUG1 was confirmed to be an miR-153 sponge. Ectopic expression of TUG1 reversed the inhibitory effect of miR-153 on the proliferation and invasion of osteosarcoma cells. Further transplantation experiments proved the carcinogenesis of TUG1 in osteosarcoma in vivo. Collectively, our study elucidated that TUG1 contributes to the development of osteosarcoma by sponging miR-153. These findings may provide a novel lncRNA-targeted therapy for patients with osteosarcoma.
Assuntos
Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Neoplasias Ósseas/genética , Proliferação de Células/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genéticaRESUMO
PURPOSE: Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has been implicated as an oncogene in the development and progression of osteosarcoma. This study aims to explore the mechanism of NEAT1 in osteosarcoma. MATERIALS AND METHODS: Expressions of NEAT1 and miR-194 in osteosarcoma tissues and cells were detected by quantitative real-time PCR. The effects of NEAT1 knockdown or miR-194 overexpression on cell proliferation, invasion, and apoptosis were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay, transwell invasive assay, and flow cytometry analysis, respectively. Luciferase reporter assay was performed to observe the possible interaction between NEAT1 and miR-194. RESULTS: NEAT1 was upregulated and miR-194 was downregulated in osteosarcoma tissues and cells. Knockdown of NEAT1 or overexpression of miR-194 suppressed proliferation and invasion and induced apoptosis of osteosarcoma cells in vitro. Luciferase reporter assay validated that NEAT1 could interact with miR-194 and negatively modulated its expression. Furthermore, inhibition of miR-194 reversed the suppression of proliferation and invasion and the promotion of apoptosis induced by NEAT1 depletion in osteosarcoma cells. CONCLUSION: Knockdown of NEAT1 suppressed proliferation and invasion and induced apoptosis in osteosarcoma cells by inhibiting miR-194 expression.