分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: C/EBP alpha is a critical transcriptional regulator of adipogenesis. HowC/EBP alpha transcriptionis itself regulated is poorly understood, however, and remains a key question that needs to be addressed for a complete understanding of adipogenic development. Here, we identify a lncRNA, ADINR(adipogenic differentiation induced noncoding RNA), transcribed from a position similar to 450 bp upstream of the C/EBP alpha gene, that orchestrates C/EBP alpha transcriptionin vivo. Depletion of ADINR leads to a severe adipogenic defect that is rescued by overexpression of C/EBP alpha. Moreover, we reveal that ADINR RNA specifically binds to PA1 and recruits MLL3/4 histone methyl-transferase complexes so as to increase H3K4me3 and decrease H3K27me3 histone modification in the C/EBP alpha locus during adipogenesis. These results show that ADINR plays important roles in regulating the differentiation of human mesenchymal stem cells into adipocytes by modulating C/EBP alpha in cis.
分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-11
摘要: Long noncoding RNAs (lncRNAs) are pervasively transcribed in the human genome. Recent studies suggest that the involvement of IncRNAs in human diseases could be far more prevalent than previously appreciated. Here we have identified a lncRNA termed Lnc_bc060912 whose expression is increased in human lung and other tumors. Lnc_bc060912 is 1.2 kb in length and is composed of two exons. The expression of Lncbc060912, was repressed by p53. Lnc_bc060912 suppressed cell apoptosis. Using a recently developed method for RNA-pulldown with formaldehyde cross-linking, we found that Lnc_bc060912 interacted With the two DNA damage repair proteins PARP1 and NPM1. Together, these results suggest that Lnc_bc060912, via PARP1 and NPM1, affects cell apoptosis and may play important roles in tumorigenesis and cancer progression.
分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-11
摘要: Esophageal Squamous Cell Carcinoma (ESCC) is among the most common malignant cancers worldwide. In the past, extensive efforts have been made to characterize the involvement of protein-coding genes in ESCC tumorigenesis but few for long noncoding RNAs (lncRNAs). To investigate the transcriptome profile and functional relevance of lncRNAs, we performed an integrative analysis of a customized combined lncRNA-mRNA microarray and RNA-seq data on ESCCs and matched normal tissues. We identified numerous lncRNAs that were differentially expressed between the normal and tumor tissues, termed "ESCC-associated lncRNAs (ESCALs)", of which, the majority displayed restricted expression pattern. Also, a subset of ESCALs appeared to be associated with ESCC patient survival. Gene set enrichment analysis (GSEA) further suggested that over half of the ESCALs were positively- or nelgativelyassociated with metastasis. Among these, we identified a novel nuclear-retained lncRNA, named Epist, which is generally highly expressed in esophagus, and which is down-regulated during ESCC progression. Epist over-expression and knockdown studies further suggest that Epist inhibits the metastasis, acting as a tumor suppressor in ESCC. Collectively, our analysis of the ESCC transcriptome identified the potential tumor suppressing lncRNA Epist, and provided a foundation for future efforts to identify functional lncRNAs for cancerous therapeutic targeting.
分类: 核科学技术 >> 核材料与工艺技术 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: This study was to evaluate effect of 125I brachytherapy combined with chemotherapy on advanced non-small cell lung cancer (NSCLC). Patients with NSCLC in stages III to IV were divided into two groups: Group A (n=27) received 125I brachytherapy combined with gemcitabine and cisplatin (GP) chemotherapy, and Group B (n=27) received GP chemotherapy only. The results showed that the overall response rate and median progression-free survival time were 78% and 11.5 months in Group A, 41% and 8 months in Group B, respectively (PP>0.05). The interventional complications in Group A included 5 patients with postoperative pneumothorax and 4 patients with hemoptysis. No patients had radiation pneumonia, radiation esophagitis or esophagotracheal fistula. Chemotherapy treatment-related toxicities were not significantly different between the two groups. The relief of tumor-associated symptoms including cough, hemoptysis, chest pain, and short breath was found in both groups, without statistical difference in remission rates between Groups A and B (P>0.05). In conclusion, 125I brachytherapy combined with chemotherapy proved to be safe and effective for treating advanced NSCLC with few complications. It improves local control rate and prolongs the progression-free survival time.