Earlier age at menarche is a major risk factor for breast cancer. Our previous study identified Nrip1 (also known as Rip140) as a candidate gene for delaying female sexual maturation (FSM) and found that knocking out Nrip1 could significantly delay FSM in mice. To investigate the effects of NRIP1 in breast cancer we used human cell lines and tissue arrays along with an in vivo study of DMBA-induced carcinogenesis in Nrip1 knockout mice. Analysis of tissue arrays found that NRIP1 is elevated in tumors compared to cancer adjacent normal tissue. Interestingly, in benign tumors NRIP1 levels are higher in the cytosol of stromal cells, but NRIP1 levels are higher in the nuclei of epithelial cells in malignancies. We also found overexpression of NRIP1 in breast cancer cell lines, and that suppression of NRIP1 by siRNA in these cells significantly induced apoptosis and inhibited cell growth. Furthermore, in vivo data suggests that NRIP1 is upregulated in DMBA-induced breast cancer. Importantly, we found that DMBA-induced carcinogenesis is suppressed in Nrip1 knockdown mice. These findings suggest that NRIP1 plays a critical role in promoting the progression and development of breast cancer and that it may be a potential therapeutic target for the new breast cancer treatments.

Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of lowdensity lipoprotein. PCSK9, which promotes the degradation of low-density lipoprotein receptors and, therefore, the increased concentration of circulating low-density lipoprotein, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying small interfering RNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients and imiquimod-induced psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated mice, and we also used cultured human keratinocytes to investigate the role of PCSK9 in regulating cell proliferation and apoptosis. We found that PCSK9 is overexpressed in psoriatic lesions and that suppressing Pcsk9 can decrease the inflammatory reaction induced by imiquimod treatment and inhibit hyperproliferation of keratinocytes. We also found that suppressing PCSK9 can significantly alter the cell cycle and induce apoptosis of human keratinocytes. Taken together, our findings indicate that PCSK9 plays an important role in psoriasis and may be a therapeutic target.

Pancreatic cancer (PC) is a fatal disease with a high mortality and poor prognosis. PC is the fourth leading cause of cancer death in America, and 80 % of PCs are diagnosed at an unresectable stage. Effective early detection assays are crucial since a successful operation at early stage is the best strategy for this disease. S100 calcium-binding protein P (S100P) has been reported as a predictive diagnostic index for PC and involves in the development of PC. However, the diagnostic accuracy of S100P in detecting PC has never been systematically assessed. The aim of the present study was to evaluate the diagnostic performance of S100P for PC. All relevant original articles about S100P in the diagnosis of PC published up to December 2013 were retrieved. The methodological quality of each study was assessed by QUADAS. The overall diagnostic sensitivity, specificity, diagnostic odds ratio (DOR), with 95 % confidence interval (CI), and area under the receiver operating characteristic curve (AUC) were pooled to evaluate the diagnostic value of S100P for PC using the Meta-DiSc1.4 statistical software. Eight studies met our criteria in the present meta-analysis. The pooled sensitivity, specificity, and DOR calculated by the bivariate random effects model were 0.87 (95 % CI 0.83-0.90), 0.88 (95 % CI 0.82-0.93), and 38.32 (95 % CI 11.22-130.87), respectively. The summary receiver operating characteristic (SROC) curve was located near the desirable left corner and the AUC was 0.9272. The current evidence suggests that S100P plays an important role in the diagnosis of PC with a high sensitivity and specificity. S100P may be regarded as a promising diagnostic marker to PC screening.

Using age of female sexual maturation as a biomarker, we previously identified nuclear receptor interacting protein 1 (Nrip1) as a candidate gene that may regulate aging and longevity. In the current report, we found that the deletion of Nrip1 can significantly extend longevity of female mice (log-rank test, p = .0004). We also found that Nrip1 expression is altered differently in various tissues during aging and under diet restriction. Remarkably, Nrip1 expression is elevated with aging in visceral white adipose tissue (WAT), but significantly reduced after 4 months of diet restriction. However, in gastrocnemius muscle, Nrip1 expression is significantly upregulated after the diet restriction. In mouse embryonic fibroblasts, we found that the deletion of Nrip1 can suppress fibroblast proliferation, enhance autophagy under normal culture or amino acid starvation conditions, as well as delay oxidative and replicative senescence. Importantly, in WAT of old animals, the deletion of the Nrip could significantly upregulate autophagy and reduce the number of senescent cells. These results suggest that deleting Nrip1 can extend female longevity, but tissue-specific deletion may have varying effects on health span. The deletion of Nrip1 in WAT may delay senescence in WAT and extend health span.

Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co-regulator for various transcriptional factors and nuclear receptors, and has been shown to take part in many biological and pathological processes, such as regulating mammary gland development and inflammatory response.The aim of this study is to investigate the expression of NRIP1 and to explore its roles in the pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1 and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions and normal controls, and also overexpressed in peripheral blood mononuclear cell (PBMCs) of psoriasis patients. Suppression of NRIP1 in HaCaT cells could significantly inhibit cell growth and induce apoptosis, and the suppression of NRIP1 in CD4+ T cells isolated from psoriasis patients could downregulate the expression of RelA/p65 and decrease the secretion of IL-17. Furthermore, in Nrip1 knockout mice, IMQ-induced inflammation of skin was delayed and the RelA/p65 expression in lesions was reduced. In conclusion, our data suggests that NRIP1 is overexpressed both in skin and PBMCs of psoriasis patients and may be involved in the abnormal proliferation and apoptosis of keratinocytes, as well as the immune reaction through the regulation of RelA/p65. Therefore, NRIP1 may be a potential therapeutic target for psoriasis.