[Effects of CSN4 knockdown on proliferation and apoptosis of breast cancer MDA-MB-231 cells].

Breast cancer is one of the most common malignant tumors endangering women. It has been found that the subunits of the COP9 complex are closely related to the occurrence and development of malignant tumors, and the CSN4 subunit plays an important role in regulating the whole complex. In the breast cancer cell line MDA-MB-231, we successfully established a lentivirus-mediated CSN4-knockdown cell line. CCK8 cell proliferation assays and colony formation experiments confirmed that CSN4 knockdown significantly decreased the cellular proliferation rate. Cell cycle analysis showed that CSN4 knockdown increased sub-G1 population and induced apoptosis. In addition, Western blotting assays confirmed that CSN4 regulates the expression of CDK6 and Caspase3, suggesting that CSN4 modulates the proliferation and apoptosis of breast cancer cells by regulating the expression of CDK6 and Caspase3 genes and thereby tumorigenesis. This study has deepened our understanding of the molecular mechanism of apoptosis and cell growth in breast cancers, and further revealed the role and mechanism of CSN4 in cancer biology.

[New polymorphic microsatellite loci identified using genomic resource for Schistosoma japonicum].

OBJECTIVE: To identify new microsatellite loci from genome sequence database for the study of polymorphism of Schistosoma japonicum. METHODS: Schistosoma japonicum isolates were obtained from seven endemic sites in China: Tongling and Guichi counties of Anhui Province, Duchang county of Jiangxi Province, Changde and Yueyang Cities of Hunan Province, Shashi City of Hubei Province, Xichang City of Sichuan Province. In order to study the genetic variance, genomic DNAs of 96 individual adult worms were screened against 17 new Schistosoma japonicum microsatellites and the raw data were analyzed by GenMapper 4.0. Furthermore, the varieties of alleles were inverstigated using GenA1Ex 6 and genetic distances within a subpopulation (GenClone) and among populations(UPGMA, MEGA 3.1) were analyzed. RESULTS: High levels of polymorphism were found between and within population samples, and significant genetic diversity was observed among the seven subpopulations. Within Jiangxi population, most genetic distances (17 loci) among samples range from 25 to 32, indicating a significant genetic diversity. There are three clusters among the seven populations: Jiangxi, Tonglin, Shashi and Changde population, with the genetics distances ranging from 0.0178 to 0.0363; Guichi and Yueyang population belong to another cluster, with the genetic distance of 0.0247; However, Xichang population is an unique group. Its genetic distances to other populations are notable with a range from 0.019 2 to 0.069 3. CONCLUSION: The 17 new polymorphic microsatellites identified may be used as suitable markers for the study on population genetics of Schistosoma japonicum and the genetic variance of the worms seems to be complicated.

Variant-type PML-RAR(alpha) fusion transcript in acute promyelocytic leukemia: use of a cryptic coding sequence from intron 2 of the RAR(alpha) gene and identification of a new clinical subtype resistant to retinoic acid therapy.

The physiologic actions of retinoic acids (RAs) are mediated through RA receptors (RARs) and retinoid X receptors (RXRs). The RAR(alpha) gene has drawn particular attention because it is the common target in all chromosomal translocations in acute promyelocytic leukemia (APL), a unique model in cancer research that responds to the effect of RA. In the great majority of patients with APL, RAR(alpha) is fused to the PML gene as a result of the t(15;17) translocation. Three distinct types of PML-RAR(alpha) transcripts, long (L), short (S), and variant (V), were identified. The V-type is characterized by truncation of exon 6 of PML and in some cases by the insertion of a variable "spacer" sequence between the truncated PML and RAR(alpha) mRNA fusion partners, although the precise mechanisms underlying formation of the V-type transcript remain unclear. To get further insights into the molecular basis of the t(15;17), we sequenced the entire genomic DNA region of RAR(alpha). Of note, all previously reported "spacer" sequences in V-type transcripts were found in intron 2 of the RAR(alpha) gene and most of these sequences were flanked by gt splice donor sites. In most cases, these "cryptic" coding sequences maintained the ORF of the chimeric transcript. Interestingly, two cases with a relatively long spacer sequence showed APL cellular and clinical resistance to RA treatment. In these cases, the aberrant V-type PML-RAR(alpha) protein displayed increased affinity to the nuclear corepressor protein SMRT, providing further evidence that RA exerts the therapeutic effect on APL through modulation of the RAR-corepressor interaction. Finally, among patients with the L- or S-type PML-RAR(alpha) fusion transcript, some consensus motifs were identified at the hotspots of the chromosome 17q breakpoints within intron 2 of RAR(alpha), strengthening the importance of this intron in the molecular pathogenesis of APL.

Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing.

Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen.