Autophagy and liver cancer

Xiaojuan Chao,Hui Qian,Shaogui Wang,Sam Fulte,Wen-Xing Ding 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.4

Autophagy is a highly conserved catabolic process that degrades cytosolic proteins and organelles via formation of autophagosomes that fuse with lysosomes to form autolysosomes, whereby autophagic cargos are degraded. Numerous studies have demonstrated that autophagy plays a critical role in the regulation of liver physiology and homeostasis, and impaired autophagy leads to the pathogenesis of various liver diseases such as viral hepatitis, alcohol associated liver diseases (AALD), non-alcoholic fatty liver diseases (NAFLD), and liver cancer. Recent evidence indicates that autophagy may play a dual role in liver cancer: inhibiting early tumor initiation while promoting progression and malignancy of already formed liver tumors. In this review, we summarized the progress of current understanding of how hepatic viral infection, alcohol consumption and diet-induced fatty liver diseases impair hepatic autophagy. We also discussed how impaired autophagy promotes liver tumorigenesis, and paradoxically how autophagy is required to promote the malignancy and progression of liver cancer. Understanding the molecular mechanisms underlying how autophagy differentially affects liver cancer development and progression may help to design better therapeutic strategies for prevention and treatment of liver cancer.

A modified RBSM for simulating the failure process of RC structures

Chao Zhao,Xingu Zhong,Bo Liu,Xiaojuan Shu,Mingyan Shen 사단법인 한국계산역학회 2018 Computers and Concrete, An International Journal Vol.21 No.2

In this paper, a modified rigid body spring model (RBSM) is proposed and used to analyze the damage and failure process of reinforced concrete (RC) structures. In the proposed model, the concrete is represented by an assembly of rigid blocks connected with a uniform distribution of normal and tangential springs to simulate the macroscopic mechanical behavior of concrete. Steel bars are evenly dispersed into rigid blocks as a kind of homogeneous axial material, and an additional uniform distribution of axial and dowel springs is defined to consider the axial stiffness and dowel action of steel bars. Perfect bond between the concrete and steel bars is assumed, and tension stiffening effect of steel bars is modeled by adjusting the constitutive relationship for the tensile reinforcement. Adjacent blocks are allowed to separate at the contact interface, which makes it convenient and easy to simulate the cracking process of concrete. The failure of the springs is determined by the Mohr-Coulomb type criterion with the tension and compression caps. The effectiveness of the proposed method is confirmed by elastic analyses of a cantilever beam under different loading conditions and failure analyses of a RC beam under two-point loading.

Uniqueness and Value-sharing of Entire Functions

Li, Xiaojuan,Meng, Chao Department of Mathematics 2009 Kyungpook mathematical journal Vol.49 No.4

In this paper, we study the uniqueness problems on entire functions sharing one value. We improve and generalize some previous results of Zhang and Lin [11]. On the one hand, we consider the case for some more general differential polynomials $[f^nP(f)]^{(k)}$ where $P({\omega})$ is a polynomial; on the other hand, we relax the nature of sharing value from CM to IM.

SLC39A10 promotes malignant phenotypes of gastric cancer cells by activating the CK2-mediated MAPK/ERK and PI3K/AKT pathways

Ren Xiaojuan,Feng Chao,Wang Yubo,Chen Pu,Wang Simeng,Wang Jianling,Cao Hongxin,Li Yujun,Ji Meiju,Hou Peng 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Solute carrier family 39 member 10 (SLC39A10) belongs to a subfamily of zinc transporters and plays a key role in B-cell development. Previous studies have reported that its upregulation promotes breast cancer metastasis by enhancing the influx of zinc ions (Zn2+); however, its role in gastric cancer remains totally unclear. Here, we found that SLC39A10 expression was frequently increased in gastric adenocarcinomas and that SLC39A10 upregulation was strongly associated with poor patient outcomes; in addition, we identified SLC39A10 as a direct target of c-Myc. Functional studies showed that ectopic expression of SLC39A10 in gastric cancer cells dramatically enhanced the proliferation, colony formation, invasiveness abilities of these gastric cancer cells and tumorigenic potential in nude mice. Conversely, SLC39A10 knockdown inhibited gastric cancer cell proliferation and colony formation. Mechanistically, SLC39A10 exerted its carcinogenic effects by increasing Zn2+ availability and subsequently enhancing the enzyme activity of CK2 (casein kinase 2). As a result, the MAPK/ERK and PI3K/AKT pathways, two major downstream effectors of CK2, were activated, while c-Myc, a downstream target of these two pathways, formed a vicious feedback loop with SLC39A10 to drive the malignant progression of gastric cancer. Taken together, our data demonstrate that SLC39A10 is a functional oncogene in gastric cancer and suggest that targeting CK2 is an alternative therapeutic strategy for gastric cancer patients with high SLC39A10 expression.

A 3-D RBSM for simulating the failure process of RC structures

Xingu Zhong,Chao Zhao,Bo Liu,Xiaojuan Shu,Mingyan Shen 국제구조공학회 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.65 No.3

Rigid body spring method (RBSM) is an effective tool to simulate the cracking process of structures, and has been successfully applied to investigate the behavior of reinforced concrete (RC) members. However, the theoretical researches and engineering applications of this method mainly focus on two-dimensional problems as yet, which greatly limits its applications in actual engineering projects. In this study, a three-dimensional (3-D) RBSM for RC structures is proposed. In the proposed model, concrete, reinforcing steels, and their interfaces are represented as discrete entities. Concrete is partitioned into a collection of rigid blocks and a uniform distribution of normal and tangential springs is defined along their boundaries to reflect its material properties. Reinforcement is modeled as a series of bar elements which can be freely positioned in the structural domain and irrespective of the mesh geometry of concrete. The bond-slip characteristics between reinforcing steel and concrete are also considered by introducing special linkage elements. The applicability and effectiveness of the proposed method is firstly confirmed by an elastic T-shape beam, and then it is applied to analyze the failure processes of a Z-type component under direct shear loading and a RC beam under two-point loading.

2-D meso-scale complex fracture modeling of concrete with embedded cohesive elements

Mingyan Shen,Zheng Shi,Chao Zhao,Xingu Zhong,Bo Liu,Xiaojuan Shu 사단법인 한국계산역학회 2019 Computers and Concrete, An International Journal Vol.24 No.3

This paper has presented an effective and accurate meso-scale finite element model for simulating the fracture process of concrete under compression-shear loading. In the proposed model, concrete is parted into four important phases: aggregates, cement matrix, interfacial transition zone (ITZ), and the initial defects. Aggregate particles were modelled as randomly distributed polygons with a varying size according to the sieve curve developed by Fuller and Thompson. With regard to initial defects, only voids are considered. Cohesive elements with zero thickness are inserted into the initial mesh of cement matrix and along the interface between aggregate and cement matrix to simulate the cracking process of concrete. The constitutive model provided by ABAQUS is modified based on Wang’s experiment and used to describe the failure behaviour of cohesive elements. User defined programs for aggregate delivery, cohesive element insertion and modified facture constitutive model are developed based on Python language, and embedded into the commercial FEM package ABAQUS. The effectiveness and accuracy of the proposed model are firstly identified by comparing the numerical results with the experimental ones, and then it is used to investigate the effect of meso-structure on the macro behavior of concrete. The shear strength of concrete under different pressures is also involved in this study, which could provide a reference for the macroscopic simulation of concrete component under shear force.

A 3-D RBSM for simulating the failure process of RC structures

Zhong, Xingu,Zhao, Chao,Liu, Bo,Shu, Xiaojuan,Shen, Mingyan Techno-Press 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.65 No.3

Rigid body spring method (RBSM) is an effective tool to simulate the cracking process of structures, and has been successfully applied to investigate the behavior of reinforced concrete (RC) members. However, the theoretical researches and engineering applications of this method mainly focus on two-dimensional problems as yet, which greatly limits its applications in actual engineering projects. In this study, a three-dimensional (3-D) RBSM for RC structures is proposed. In the proposed model, concrete, reinforcing steels, and their interfaces are represented as discrete entities. Concrete is partitioned into a collection of rigid blocks and a uniform distribution of normal and tangential springs is defined along their boundaries to reflect its material properties. Reinforcement is modeled as a series of bar elements which can be freely positioned in the structural domain and irrespective of the mesh geometry of concrete. The bond-slip characteristics between reinforcing steel and concrete are also considered by introducing special linkage elements. The applicability and effectiveness of the proposed method is firstly confirmed by an elastic T-shape beam, and then it is applied to analyze the failure processes of a Z-type component under direct shear loading and a RC beam under two-point loading.

Differential Sensitivity of Target Genes to Translational Repression by miR-17~92

Jin, Hyun Yong,Oda, Hiroyo,Chen, Pengda,Yang, Chao,Zhou, Xiaojuan,Kang, Seung Goo,Valentine, Elizabeth,Kefauver, Jennifer M.,Liao, Lujian,Zhang, Yaoyang,Gonzalez-Martin, Alicia,Shepherd, Jovan,Morgan, Public Library of Science 2017 PLoS genetics Vol.13 No.2

<▼1><P>MicroRNAs (miRNAs) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree, but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA. Here, we conducted an integrated analysis of transcriptome and translatome of primary B cells from mutant mice expressing miR-17~92 at three different levels to address this issue. We found that target genes exhibit differential sensitivity to miRNA suppression and that only a small fraction of target genes are actually suppressed by a given concentration of miRNA under physiological conditions. Transgenic expression and deletion of the same miRNA gene regulate largely distinct sets of target genes. miR-17~92 controls target gene expression mainly through translational repression and 5’UTR plays an important role in regulating target gene sensitivity to miRNA suppression. These findings provide molecular insights into a model in which miRNAs exert their specific functions through a small number of key target genes.</P></▼1><▼2><P><B>Author summary</B></P><P>MicroRNAs (miRNAs) are small RNAs encoded by our genome. Each miRNA binds hundreds of target mRNAs and performs specific functions. It is thought that miRNAs exert their function by reducing the expression of all these target genes and each to a small degree. However, these target genes often have very diverse functions. It has been unclear how small changes in hundreds of target genes with diverse functions are translated into the specific function of a miRNA. Here we take advantage of recent technical advances to globally examine the mRNA and protein levels of 868 target genes regulated by miR-17~92, the first oncogenic miRNA, in mutant mice with transgenic overexpression or deletion of this miRNA gene. We show that miR-17~92 regulates target gene expression mainly at the protein level, with little effect on mRNA. Surprisingly, only a small fraction of target genes respond to miR-17~92 expression changes. Further studies show that the sensitivity of target genes to miR-17~92 is determined by a non-coding region of target mRNA. Our findings demonstrate that not every target gene is equal, and suggest that the function of a miRNA is mediated by a small number of key target genes.</P></▼2>