Cancer has become a major disease burden across the globe. It was estimated that 4.29 million new incident cases and 2.81 million death cases of cancer would occur in 2015 in China, with the age-standardized incidence rate (ASIR) of 201.1 per 100,000 and age-standardized mortality rate (ASMR) of 126.9 per 100,000, respectively. For females, 2 of the top 10 most common types of cancer would be gynecologic cancers, with breast cancer being the most prevalent (268.6 thousand new incident cases) and cervical cancer being the 7th most common cancer (98.9 thousand new incident cases). The incidence and mortality of gynecologic cancers have been constantly increasing in China over last 2 decades, which become a major health concern for women. Survival rates of gynecologic cancers are generally not satisfactory and decrease along with advancing stage, though national data on survival are still not available. It is of great importance to overview on the epidemiology of gynecologic cancers, which may provide scientific clues for strategy-making of prevention and control, and eventually lowering the incidence and mortality rate as well as improving the survival rate in the future.
Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding. Increases in mRNA level or stability of pro-inflammatory cytokines/chemokines are abolished by PARP1 ablation or inhibition, or blocked in D226A HuR-expressing cells. The present study demonstrates a mechanism to regulate gene expression at the post-transcriptional level, and suggests that blocking the interaction of PARP1 with HuR could be a strategy to treat inflammation-related diseases that involve increased mRNA stability.
Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and differentiation steps. Here we show that Isl1 acts as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which shows congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, we uncover a regulatory network downstream of Isl1 that orchestrates cardiogenesis. Mechanistically, we show that Isl1 binds to compacted chromatin and works in concert with the Brg1-Baf60c-based SWI/SNF complex to promote permissive cardiac lineage-specific alterations in the chromatin landscape not only of genes with critical functions in cardiac progenitor cells, but also of cardiomyocyte structural genes that are highly expressed when Isl1 itself is no longer present. Thus, the Isl1/Brg1-Baf60c complex plays a crucial role in orchestrating proper cardiogenesis and in establishing epigenetic memory of cardiomyocyte fate commitment.
Background: The epidemiological feature of human papillomavirus (HPV) infection is distinctive in China. We aimed to investigate the multi-infection patterns and co-infection preference of 27 HPV types among gynecological outpatients across China. Methods: Overall 137,943 gynecological outpatients were recruited from eight tertiary hospitals located in seven regions of China, between July 1st, 2014 and December 31st, 2016. The overall, region-specific, age-specific and type-specific prevalence of HPV infection were calculated, respectively. The pattern of HPV infection was also evaluated. Furthermore, rate ratio was calculated to evaluate the co-infection preference of any two HPV genotypes. Results: The overall prevalence of 27 HPVs' [17 high-risk (hr)/10 low-risk (lr)] infection was 23.5%. The age-specific HPV prevalence showed a "U-shaped" pattern. The most prevalent hrHPV genotypes were 16, 52, and 58. Multiple infections were detected in 25.8% of the HPV-positive women, in which dual infection was more prevalent. HPV 16/18 were likely to co-infected with HPV 31 but unlikely with HPV 52/58, i.e., the coinfection of HPV 16 with HPV 31 was high (3.5-fold), but low for HPV 58 (1.8-fold), and 52 (1.2-fold), while the co-infection of HPV 18 with HPV 31 was high (4.3-fold), but low for HPV 52 (1.9-fold), and 58 (1.7-fold). Conclusions: We found age-specific prevalence of HPV infection showed a "U-shaped" pattern for high and low risk HPV, suggesting the importance of screening among younger women and the necessary of detection among older women. We found a novel co-infection preference of HPV 16/18 with 31, 52, and 58, suggesting a need of developing and marketing prophylactic HPV vaccines that protect against more genotypes in China.
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