Digital Analysis of Immunostaining of ZW10 Interacting Protein in Human Lung Tissues

The purpose of this study is to introduce a methodology of the immunostaining of human lung tissues, followed by whole-slide digital scanning and image ...

wuhan university

Cancer is currently one of the leading causes of death worldwide and is one of the most challenging major public health problems. The main challenges faced by clinicians in the management and treatment of cancer mainly arise from difficulties in early diagnosis and the emergence of tumor chemoresistance and metastasis. The structures of chemokine receptor 9 (CCR9) and its specific ligand chemokine ligand 25 (CCL25) have been elucidated, and, interestingly, a number of studies have demonstrated that CCR9 is a potential tumor biomarker in diagnosis and therapy, as it has been found to be highly expressed in a wide range of cancers. This expression pattern suggests that CCR9 may participate in many important biological activities involved in cancer progression. Researchers have shown that CCR9 that has been activated by its specific ligand CCL25 can interact with many signaling pathways, especially those involved in tumor chemoresistance and metastasis. This review, therefore, focuses on CCR9 induction activity and summarizes what is currently known regarding its role in cancers and its potential application in tumor-targeted therapy.

CCR9 in cancer: oncogenic role and therapeutic targeting.

Lung cancer is the leading cause of mortalities among all types of cancer. Therefore, the screening of biomarkers that are related with the progression of lung cancer is crucial for early diagnosis and efficient therapy of lung cancer. In the present study, bioinformatic analysis identified replication factor C 5 (RFC5) as a potential novel oncogene in lung cancer. RFC5 functions as a clamp loader and is involved in DNA replication and repair. Analysis of public databases and reverse transcription-quantitative polymerase chain reaction indicated that RFC5 was significantly increased in tumor tissues compared with adjacent normal tissues. A high RFC5 expression was observed to be associated with more aggressive malignant clinicopathological features, including higher T stage, more advanced regional lymph node metastasis and a higher probability of relapse. Notably, there were notable differences in overall survival (OS), first progression and post-progression survival between the high RFC5 expression group and low RFC5 expression group. Univariate and multivariate Cox regression analyses indicated that RFC5 was an independent risk factor that was associated with poorer OS and disease-free survival. According to GSEA, several gene sets that are associated with cell cycle and DNA damage were enriched in the RFC5 overexpression group, which indicated that RFC5 might promote the proliferation of lung cancer cells. Our finding indicated that RFC5 might be a novel prognostic biomarker of lung cancer, and it might be serve as a potential diagnosis and therapy target for lung cancer in the future.

Identification of RFC5 as a novel potential prognostic biomarker in lung cancer through bioinformatics analysis.

Metastatic disease remains the primary cause of death for individuals with T cell acute lymphoblastic leukemia (T-ALL). microRNAs (miRNAs) play important roles in the pathogenesis of T-ALL by inhibiting gene expression at posttranscriptional levels. The goal of the current project is to identify any significant miRNAs in T-ALL metastasis. We observed miR-146b-5p to be downregulated in T-ALL patients and cell lines, and bioinformatics analysis implicated miR-146b-5p in the hematopoietic system. miR-146b-5p inhibited the migration and invasion in T-ALL cells. Interleukin-17A (IL-17A) was predicted to be a target of miR-146b-5p; this was confirmed by luciferase assays. Interestingly, T-ALL patients and cell lines secreted IL-17A and expressed the IL-17A receptor (IL-17RA). IL-17A/IL-17RA interactions promoted strong T-ALL cell migration and invasion responses. Gene set enrichment analysis (GSEA) and quantitative polymerase chain reaction (qPCR) analysis indicated that matrix metallopeptidase-9 (MMP9), was a potential downstream effector of IL-17A activation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was also implicated in this process. Moreover, IL-17A activation promoted T-ALL cell metastasis to the liver in IL17A  mouse models. These results indicate that reduced miR-146b-5p expression in T-ALL may lead to the upregulation of IL-17A, which then promotes T-ALL cell migration and invasion by upregulating MMP9 via NF-κB signaling.

Loss of miR-146b-5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL-17A pathway.

Two-dimensional (2D) magnetic materials provide an ideal platform for the application in spintronic devices due to their unique spin states in nanometer scale. However, recent research on the exfoliated monolayer magnetic materials suffers from the instability in ambient atmosphere, which needs extraordinary protection. Hence the controllable synthesis of 2D magnetic materials with good quality and stability should be addressed. Here we report for the first time the van der Waals (vdW) epitaxial growth of one-unit-cell-thick air-stable ferrimagnet CrS semiconductor via a facile chemical vapor deposition method. Single crystal CrS with the domain size reaching to 200 μm is achieved. Most importantly, we observe the as grown CrS with a Néel temperature ( T) of up to 120 K and a maximum saturation magnetic momentum of up to 65 μemu. As the temperature decreases, the samples show a transition from soft magnet to hard magnet with the highest coercivity of 1000 Oe. The one-unit-cell-thick CrS devices show a p-type transfer behavior with an on/off ratio over 10. Our work highlights CrS monolayer as an ideal magnetic semiconductor for 2D spintronic devices. The vdW epitaxy of nonlayered magnets introduces a new route for realizing magnetism in 2D limit and provides more application potential in the 2D spintronics.

Xiong Jie

Department of Immunology,
School of Basic Medical Sciences,
Department of Immunology, School of Basic Medical Sciences

wuhan university

Digital Analysis of Immunostaining of ZW10 Interacting Protein in Human Lung Tissues

Xiong Jie

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Immunology,School of Basic Medical Sciences,Department of Immunology, School of Basic Medical Sciences

wuhan university

Digital Analysis of Immunostaining of ZW10 Interacting Protein in Human Lung Tissues

Department of Immunology,
School of Basic Medical Sciences,
Department of Immunology, School of Basic Medical Sciences