Role of cell-cycle regulators in lung cancer

Lung cancer is the leading cause of cancer death worldwide. Histologically, 80% of lung cancers are classified as non-small-cell lung cancer (NSCLC), and the remaining 20% as small-cell lung cancer (SCLC). Lung carcinoma is the result of molecular changes in the cell, resulting in the deregulation of pathways controlling normal cellular growth, differentiation, and apoptosis. This review summarizes some of the most recent findings about the role of cell-cycle proteins in lung cancer pathogenesis and progression.     

Differential regulation in tobacco cell suspensions of genes involved in plant-bacteria interactions by pathogen-related signals

Six cDNA clones whose corresponding mRNAs accumulate early during the hypersensitive reaction in tobacco leaves have been classified into 2 groups according to their maximum levels of accumulation in an incompatible versus a compatible interaction withPseudomonas solanacearum. We present evidence that, at least in the first stages of the interaction, tobacco cell suspensions retain the ability to respond differentially to compatible and incompatible isolates ofP. solanacearum.In addition, studies on the effect of a fungal elicitor on the accumulation of the mRNAs corresponding to the cDNA clones in cell suspensions indicate that only one group of genes responds to this treatment.     

Differential regulation of cadmium-inducible expression of iron-deficiency-responsive genes in tobacco and barley

The expression of four representative iron-deficiency-responsive genes from tobacco ( NtIRT1 and NtYSL1 ) and barley ( HvIDS2 and HvYS1 ) plants were evaluated in each host plant in response to iron deficiency (ΔFe), cadmium exposure (+Cd) or both (ΔFe + Cd). These conditions significantly enhanced NtIRT1 and HvIDS2 expression in roots, whereas NtYSL1 and HvYS1 expression was similar in shoots and roots. NtIRT1 expression under +Cd and ΔFe + Cd was lower than that under ΔFe, whereas the expression of NtYSL1 , HvIDS2 and HvYS1 in roots under +Cd and ΔFe + Cd was similar or higher than that under ΔFe. A time-course experiment showed that NtIRT1 expression under +Cd and ΔFe was regulated similarly throughout the experiment [expressed between 3 and 21 days after treatment (DAT)]. NtYSL1 expression under +Cd and ΔFe began at 1 DAT; expression soon disappeared under ΔFe, whereas it continued to 21 DAT under +Cd. The timing of HvIDS2 and HvYS1 expression under +Cd (between 1 and 5 DAT) was earlier than that under ΔFe (between 5 and 21 DAT). Notably, no Fe deficit occurred in any parts of these plants when grown under +Cd, except for tobacco shoots, even when the genes were highly expressed. Thus, some expression under +Cd differed from that under ΔFe. It is possible that both the genuine Fe-deficiency-responsive mechanism and an unidentified mechanism, which can be directly regulated by Cd, contribute to gene expression to maintain metal homeostasis within the plant.     

Epigenetic regulation of miR-212 expression in lung cancer

Many studies have shown that microRNA expression in cancer may be regulated by epigenetic events. Recently, we found that in lung cancer miR-212 was strongly down-regulated. However, mechanisms involved in the regulation of miR-212 expression are unknown. Therefore, we addressed this point by investigating the molecular mechanisms of miR-212 silencing in lung cancer. We identified histone modifications rather than DNA hypermethylation as epigenetic events that regulate miR-212 levels in NSCLC. Moreover, we found that miR-212 silencing in vivo is closely associated with the severity of the disease.     

Identification and validation of key genes associated with non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is one of the main causes of death induced by cancer globally. However, the molecular aberrations in NSCLC patients remain unclearly. In the present study, four messenger RNA microarray datasets (GSE18842, GSE40275, GSE43458, and GSE102287) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NSCLC tissues and adjacent lung tissues were obtained from GEO2R and the overlapping DEGs were identified. Moreover, functional and pathway enrichment were performed by Funrich, while the protein–protein interaction (PPI) network construction were obtained from STRING and hub genes were visualized and identified by Cytoscape software. Furthermore, validation, overall survival (OS) and tumor staging analysis of selected hub genes were performed by GEPIA. A total of 367 DEGs (95 upregulated and 272 downregulated) were obtained through gene integration analysis. The PPI network consisted of 94 nodes and 1036 edges in the upregulated DEGs and 272 nodes and 464 edges in the downregulated DEGs, respectively. The PPI network identified 46 upregulated and 27 downregulated hub genes among the DEGs, and six (such as CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M) of that have not been identified to be associated with NSCLC so far. Moreover, the expression differences of the mentioned hub genes were consistent with that in lung adenocarcinoma and lung squamous cell carcinoma in the TCGA database. Further analysis showed that all the six hub genes were associated with tumor staging except MYH11, while only the upregulated DEG CENPE was associated with the worse OS of patients with NSCLC. In conclusion, the current study showed that CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M might be the key genes contributed to tumorigenesis or tumor progression in NSCLC, further functional study is needed to explore the involved mechanisms.     

Differential expression of aortic and lung elastin genes during chick embryogenesis

The ratios of tropoelastin b to a were measured in chick aorta and lung during embryogenesis. The rates of tropoelastin a and b synthesis were determined in short-term organ culture. The results demonstrated that in lung tissue the ratio of the two tropoelastins remained essentially constant. Each of the tropoelastins comprised 50% of the total elastin synthesis. In the aortic tissue, tropoelastin b represented 70% of the total elastin in the 11- to 13-day embryos and increased to 91% by Day 16. These observations seen in the organ culture system were paralleled in measurements of functional mRNAs coding for the two proteins. Measurements of functional tropoelastin mRNAs from both lung and aortic tissues were performed in a mRNA-dependent rabbit reticulocyte lysate system. Although the changes in the abundance of the tropoelastin mRNAs revealed the same trend as that seen in the organ culture data, the magnitude of the tropoelastin b to a ratio in the aortic organ culture was twice that determined in the cell-free translation of aortic mRNAs. The data obtained from both cell-free translations and organ culture experiments demonstrate that there is a differential expression of elastin genes during aorta development which is significantly different from that found in developing lung.     

NIRF,a novel RING finger protein,is involved in cell-cycle regulation

Through database mining, we found a novel PEST-containing nuclear protein (PCNP). To characterize PCNP, we carried out yeast two-hybrid screening for PCNP-interacting factors. A novel Np95/ICBP90-like RING finger protein (NIRF), which possessed a ubiquitin-like domain, a PHD finger, a YDG/SRA domain and a RING finger, was identified. Interaction between PCNP and NIRF was clarified by mammalian two-hybrid system, GST pull-down assay, and nuclear co-localization. RT-PCR showed that NIRF expression is high in proliferating phase but significantly low in G0/G1 phase in normal TIG-7 and WI-38 cells, while consistently high in tumoral HT-1080 and HepG2 cells, suggesting that NIRF is involved in cell-cycle regulation. The NIRF gene resides in 9p23-24.1 that is altered in numerous types of tumors at the top of frequency. Furthermore, the NIRF gene is just within small amplicons in some tumors, suggesting that PCNP and NIRF might be involved in some aspects of tumorigenesis.     

DSP1, an HMG-like protein, is involved in the regulation of homeotic genes

The Drosophila dsp1 gene, which encodes an HMG-like protein, was originally identified in a screen for corepressors of Dorsal. Here we report that loss of dsp1 function causes homeotic transformations resembling those associated with loss of function in the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Abdominal-B. The expression pattern of Scr is altered in dsp1 mutant imaginal discs, indicating that dsp1 is required for normal expression of this gene. Genetic interaction studies reveal that a null allele of dsp1 enhances trithorax-group gene (trx-G) mutations and partially suppresses Polycomb-group gene (Pc-G) mutations. On the contrary, overexpression of dsp1 induces an enhancement of the transformation of wings into halteres and of the extra sex comb phenotype of Pc. In addition, dsp1 male mutants exhibit a mild transformation of A4 into A5. Comparison of the chromatin structure at the Mcp locus in wild-type and dsp1 mutant embryos reveals that the 300-bp DNase I hypersensitive region is absent in a dsp1 mutant context. We propose that DSP1 protein is a chromatin remodeling factor, acting as a trx-G or a Pc-G protein depending on the considered function.     

昆虫抗药性相关细胞色素P450基因的表达调控机制

杀虫剂的频繁持续使用,必然导致昆虫产生抗药性.大量研究事例表明参与杀虫剂解毒的细胞色素P450(简称P450)过量表达是昆虫对不同类型杀虫剂产生抗性的重要原因,但目前人们对P450基因过量表达机制的认识还非常有限.近十年来,随着生命科学与相关研究技术的发展,有关昆虫P450基因表达调控机制的研究取得了实质性的进展.本文...