Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.

Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS. Bioinformatics analysis indicated that RCC1 is highly expressed and correlated with poor prognosis in STS. Functional studies showed that RCC1 knockdown significantly inhibited the cell cycle transition, proliferation and migration of STS cells in vitro, and the growth of STS xenografts in mice. Mechanistically, we identified Skp2 as a downstream target of RCC1 in STS. Loss of RCC1 substantially diminished Skp2 abundance by compromising its protein stability, resulting in the upregulation of p27Kip1 and G1/S transition arrest. Specifically, RCC1 might facilitate the nucleo-cytoplasmic trafficking of Skp2 via direct interaction. As a result, the cytoplasmic retention of Skp2 would further protect it from ubiquitination and degradation. Notably, recovery of Skp2 expression largely reversed the phenotypes induced by RCC1 knockdown in STS cells. Collectively, this study unveils a novel RCC1-Skp2-p27Kip1 axis in STS oncogenesis, which holds promise for improving prognosis and treatment of this formidable malignancy.

Unveiling the transcriptome alteration of POMC neuron in diet-induced obesity.

Loss of neuron homeostasis in the arcuate nucleus (ARC) is responsible for diet-induced-obesity (DIO). We previously reported that loss of Rb1 gene compromised the homeostasis of anorexigenic POMC neurons in ARC and induced obesity in mice. To evaluate the development of DIO, we propose to analyze the transcriptomic alteration of POMC neurons in mice following high fat diet (HFD) feeding. We isolated these neurons from established DIO mice and performed transcriptomic profiling using RNA-seq. In total, 1066 genes (628 upregulated and 438 downregulated) were identified as differentially expressed genes (DEGs). Pathway enrichment analysis with these DEGs further revealed that "cell cycle," "apoptosis," "chemokine signaling," and "sphingolipid metabolism" pathways were correlated with DIO development. Moreover, we validated that the pRb protein, a key regulator of "cell cycle pathway," was inactivated by phosphorylation in POMC neurons by HFD feeding. Importantly, the reversal of deregulated cell cycle by stereotaxic delivering of the unphosphorylated pRbΔP in ARC significantly meliorated the DIO. Collectively, our study provides insights into the mechanisms related to the loss of homeostasis of POMC neurons in DIO, and suggests pRb phosphorylation as a potential intervention target to treat DIO.

Multivariate systems of nonexpansive operator equations and iterative algorithms for solving them in uniformly convex and uniformly smooth Banach spaces with applications.

We prove some existence theorems for solutions of a certain system of multivariate nonexpansive operator equations and calculate the solutions by using the generalized Mann and Halpern iterative algorithms in uniformly convex and uniformly smooth Banach spaces. The results of this paper improve and extend the previously known ones in the literature.

A kind of system of multivariate variational inequalities and the existence theorem of solutions.

Let K be a nonempty closed convex and bounded subset of a reflexive Banach space X. Let [Formula: see text] be N-variables monotone demi-continuous mappings from [Formula: see text] into X. Then: (1) the system of multivariate variational inequalities [Formula: see text] has a solution [Formula: see text]; (2) the set of solutions of this system of multivariate variational inequalities is closed convex in [Formula: see text]; (3) if [Formula: see text] are also strictly monotone, this system of multivariate variational inequalities has a unique solution.

Multidirectional hybrid algorithm for the split common fixed point problem and application to the split common null point problem.

In this article, a new multidirectional monotone hybrid iteration algorithm for finding a solution to the split common fixed point problem is presented for two countable families of quasi-nonexpansive mappings in Banach spaces. Strong convergence theorems are proved. The application of the result is to consider the split common null point problem of maximal monotone operators in Banach spaces. Strong convergence theorems for finding a solution of the split common null point problem are derived. This iteration algorithm can accelerate the convergence speed of iterative sequence. The results of this paper improve and extend the recent results of Takahashi and Yao (Fixed Point Theory Appl 2015:87, 2015) and many others .

On an open question of V. Colao and G. Marino presented in the paper "Krasnoselskii-Mann method for non-self mappings".

Let H be a Hilbert space and let C be a closed convex nonempty subset of H and [Formula: see text] a non-self nonexpansive mapping. A map [Formula: see text] defined by [Formula: see text]. Then, for a fixed [Formula: see text] and for [Formula: see text], Krasnoselskii-Mann algorithm is defined by [Formula: see text] where [Formula: see text]. Recently, Colao and Marino (Fixed Point Theory Appl 2015:39, 2015) have proved both weak and strong convergence theorems when C is a strictly convex set and T is an inward mapping. Meanwhile, they proposed a open question for a countable family of non-self nonexpansive mappings. In this article, authors will give an answer and will prove the further generalized results with the examples to support them.

On the best proximity point for the proximal contractive and nonexpansive mappings on the starshaped sets.

The purpose of this paper is to the best proximity point theorems for the proximal nonexpansive mapping on the starshaped sets by using a clever and simple method. The results improve and extend the recent results of Chen et al. (Fixed Point Theory Appl 2015:19, 2015). It should be noted that, the complex method is used by Jianren Chen et al. can be replaced by the clever and simple method presented in this paper.

ψ-Contraction and [Formula: see text]-contraction in Menger probabilistic metric space.

The purpose of this paper is to present the definition of [Formula: see text]-contractive mapping and to discuss the relation of [Formula: see text]-contractive mappings and [Formula: see text]-contractive mappings. Furthermore, the generalized [Formula: see text]-contraction mapping principle has been proved without the uniqueness condition. Meanwhile, the generalized [Formula: see text]-contraction mapping principle has been obtained by using an ingenious method.