RESUMO
Oncofetal genes are genes that express abundantly in both fetal and tumor tissues yet downregulated or undetected in adult tissues, and can be used as tumor markers for cancer diagnosis and treatment. Meanwhile, long noncoding RNAs (lncRNAs) are known to play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC), including tumor growth, proliferation, metastasis, invasion, and recurrence. We performed a genome-wide screening using microarrays to detect the lncRNA expression profiles in fetal livers, adult livers, and liver cancer tissues from mice to identify oncofetal lncRNAs in HCC. From the microarray data analysis, we identified lncRNA Ptn-dt as a possible oncofetal gene. Both in vitro and in vivo experiments results confirmed that overexpression of Ptn-dt significantly promoted the proliferation of mouse HCC cells. RNA pulldown assay showed that Ptn-dt could interact with the HuR protein. Interestingly, miR-96 binds with HuR to maintain its stability as well. Overexpression of lncRNA Ptn-dt led to the downregulation of miR-96, which might be due to the interaction between Ptn-dt and HuR. Meanwhile, previous studies have reported that Ptn can promote tumor growth and vascular abnormalization via anaplastic lymphoma kinase (Alk) signaling. In our study, we found that overexpression of Ptn-dt could promote the expression of Alk through repressing miR-96 via interacting with HuR, thus enhancing the biologic function of Ptn. In summary, a new oncofetal lncRNA Ptn-dt is identified, and it can promote the proliferation of HCC cells by regulating the HuR/miR-96/Alk pathway and Ptn-Alk axis.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Proliferação de Células/genética , Citocinas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Quinase do Linfoma Anaplásico/genética , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Regulação para Baixo , Estudo de Associação Genômica Ampla/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: To study the relationship between the percentage of polypronuclear zygotes and clinical pregnancy following IVF. METHODS: We collected the data of 954 IVF cycles, and according the percentage of polypronuclear zygotes in the IVF cycles, allocated them to Groups A (without polypronuclear zygotes) , B (with < 30% polypronuclear zygotes) and C (with > or = 30% polypronuclear zygotes). Then we analyzed the relationship between the percentage of polypronuclear zygotes and the rate of clinical pregnancy. RESULTS: Compared with Group A, Group C showed a significantly lower rate of clinical pregnancy (43.2% vs 28. 1%, P < 0.05), while Group B exhibited a markedly higher rate (43.2% vs 52.36%, P < 0.05) and obviously decreased polypronuclear zygote formation with the increase of age (35.6% vs 24.1%, P < 0.05). CONCLUSION: The percentage of polypronuclear zygotes in IVF cycles may serve as a prognostic indicator of the clinical outcome.
