No abstract

Much recent attention has been focused on Aurora C, the third member of the mammalian Aurora kinases family that plays significant roles in mitosis. We report here that using sensitive RT-PCR to amplify the C-terminal, we found that Aurora C is not only expressed highly in testis, but also among 16 other human tissues in a broad-spectrum way. Aurora C, as a chromosomal passenger protein, is co-localized with Aurora B and Survivin in mitotic cells. Aurora C can also be associated with Aurora B and Survivin in vivo and directly binds to Survivin but not Aurora B in vitro . Overexpression of a catalytically inactive mutant of Aurora C impaired the localization of Aurora C to the spindle midzone and severely disturbed the cytokinesis, resulting in multinucleation, all of which are consistent with the results induced by the mutant of Aurora B. Furthermore, we provide evidence that Aurora C could rescue the multinucleate phenotype produced by Aurora B mutant, and vice versa. Overall, these findings demonstrate that Aurora C, a member of the chromosomal passenger complex, is required for cytokinesis.

Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.

No abstract

Activation of cyclin E1, a key regulator of the G1/S cell-cycle transition, has been implicated in many cancers including hepatocellular carcinoma (HCC). Although much is known about the regulation of cyclin E1 expression and stability, its post-transcriptional regulation mechanism remains incompletely understood. Here, we report that nuclear factor 90 (NF90), a double-stranded RNA (dsRNA) binding protein, regulates cyclin E1 in HCC. We demonstrate that NF90 is upregulated in HCC specimens and that suppression of NF90 decreases HCC cell growth and delays G1/S transition. We identified cyclin E1 as a new target of NF90 and found a significant correlation between NF90 and cyclin E1 expression in HCC. The mRNA and protein levels of cyclin E1 were downregulated upon NF90 knockdown. Suppression of NF90 caused a decrease in the half-life of cyclin E1 mRNA, which was rescued by ectopic expression of NF90. Furthermore, NF90 bound to the 3′ untranslated regions (3′UTRs) of cyclin E1 mRNA in vitro and in vivo. Knockdown of NF90 also inhibited tumor growth of HCC cell lines in mouse xenograft model. Moreover, we showed that inhibition of NF90 sensitized HCC cells to the cyclin-dependent kinase 2 (CDK2) inhibitor, roscovitine. Taken together, downregulation of NF90 in HCC cell lines can delay cell-cycle progression, inhibit cell proliferation, and reduce tumorigenic capacity in vivo. These results suggest that NF90 has an important role in HCC pathogenesis and that it can serve as a novel therapeutic target for HCC.